NeuroMedix Poised to Realize Next Stage of Business Plan through Strategic Alliance or Acquisition

NewswireToday - /newswire/ - Toronto, ON, Canada, 11/30/2006 - Neuromedix has made important progress in the cure of Alzheimer's disease, and is planning for the next phase of product development through strategic alliance or acquisition

NeuroMedix Inc. (“NeuroMedix” or the “Company”) (TSXV: NMX) today announced that based on the positive pre-clinical development data received to date for its lead product, Minozac, it will now explore licensing or acquisition transactions with a view to maximizing shareholder value.

“As we complete the final stages of our pre-clinical development program and prepare towards the submission of our Phase I safety application to the regulatory authorities, our Board of Directors has directed management to seek strategic alliances with pharmaceutical and biotechnology partners and to explore merger and acquisition transactions”, said Dr. Mark L. Pearson, Chief Executive Officer, “Consistent with our business strategy, we plan to seek partners or acquirers with the financial resources to further advance the clinical development of Minozac in a bid to ensure Minozac’s rapid development to benefit patients with Alzheimer’s and other neuroinflammatory brain indications. Our Board has assessed Minozac’s commercial potential in several large markets, including the treatment of Alzheimer’s disease, and believes this path will maximize value to NeuroMedix shareholders.”

As a first step in this business strategy, NeuroMedix plans to complete an interim financing before the end of the year.

NeuroMedix provides no assurance that the implementation of a process to explore licensing or acquisition transactions with a view to maximizing shareholder value will result in a transaction. No decision has been made to enter into any transaction at this time. The Company will retain investment bankers to provide financial advice to NeuroMedix in this process.

About NeuroMedix

NeuroMedix is a biotechnology company focused on the development of therapeutic agents for the treatment of degenerative and inflammatory diseases of the central nervous system, such as Alzheimer’s disease, traumatic brain injury, neuropathic pain, age-related macular degeneration and multiple sclerosis. Our therapeutic drug candidates are based on research from a team of leading experts in the field of neuroinflammation at Northwestern University and have been demonstrated to reduce brain inflammation, to protect neuronal cells, and to prevent the loss of cognitive function in an Alzheimer’s disease animal model in mice. Our lead candidate, Minozac has also been shown to reduce inflammation and prevent loss of cognitive function in mice suffering traumatic brain injury. Based on these findings, NeuroMedix is pursuing the development of its lead compound for Alzheimer’s disease and traumatic brain injury in humans. NeuroMedix’s shares are listed on the TSX Venture Exchange under the symbol “NMX”.

Weekly Monitor Drug and Diagnostic Development in Neurodegenerative Diseases

HiTIS - life science & biotech intelligence, a European life sciences industry focused competitive intelligence firm, recently launched Neurodegenerative Diseases Therapeutics & Diagnostics Competitive Intelligence Weekly


Courbevoie, France, November 30, 2006 --(PR.COM)-- HiTIS – life science & biotech intelligence, a European life sciences industry focused competitive intelligence firm, added recently a neurodegenerative diseases therapies-focused publication to its growing family of periodical competitive intelligence reports.

Neurodegenerative Diseases Therapeutics & Diagnostics Competitive Intelligence is a weekly publication reporting industry and academy news in a digital format. The reports cover the whole life cycle of drugs and diagnostics addressing those diseases, from lab-bench to patients, via regulatory authorities.

Drugs and diagnostics (existing and candidates) which are monitored address most frequent neurodegenerative diseases (Alzheimer, Parkinson, Multiple Sclerosis, Huntington, Amyotrophic Lateral Sclerosis) as well as rare disorders (eg. Batten, Menkes, Pick, Sandhoff, Adrenomyeloneuropathy etc.).

“What we are looking for with these publications is to provide pharma, biopharma, biotech and diagnostics industry decision-makers with a unique, synthetic and global source of competitive intelligence data. Time is money, and costs associated with the collection of this information can be tremendous,” said Christian Girard.

He added, “Our news center daily collects, filters, sorts and saves industry and academy primary information, avoiding press redundancy and delays. The publications are derived products. Each report is divided into several parts, following the homepage introducing mentioned companies and institutions: All News, Regulatory, Research, Preclinical, Clinical, Products, Funding, Financial, Deals, Litigation and IP. Links to companies’ websites and full-text releases are included.”

A recent issue of this publication can be viewed at:

http://www.txpreview.com/NCI%20Weekly%20-%20%20Y2006%20W43.htm


About HiTIS Competitive Intelligence Publications

HiTIS Competitive Intelligence Publications family includes several focused electronic publications covering therapeutic fields or technologies, like:

Vaccines Competitive Intelligence Weekly, Neurodegenerative Diseases Tx/Dx Competitive Intelligence Weekly, and Eye Therapies Competitive Intelligence Weekly.

Other similar publications will be announced in due time. Note that specific, customized publications may be developed upon request.

About HiTIS - life science & biotech intelligence

HiTIS - life science & biotech intelligence is a European competitive intelligence firm offering various intelligence resources and tools: a web-based competitive intelligence platform, customized R&D Pipelines, and a series of periodical competitive intelligence publications.

A free of charge 7-day news center trial and reports samples are available on request: see www.txpreview.com for more information

Contact

Christian Girard
Founding Partner & Editor
Mobile +33 (0)6 67 26 60 92
Office +33 (0)1 47 88 23 48
christian.girard@biotech-intelligence.com
www.biotech-intelligence.com and www.txpreview.com
HiTIS - life science & biotech intelligence
11, rue Madiraa - 92400 Courbevoie - France

###
Contact Information
HiTIS - life science & biotech intelligence
Christian Girard
33 147 882 348
christian.girard@biotech-intelligence.com
www.txpreview.com

Men increasingly becoming caregivers

AS BOOMERS AGE, BOTH SEXES KEEP AILING FAMILY AT HOME
By Jonathan Peterson
LOS ANGELES TIMES

WEST CHESTER, Pa. - Joe Wolf still remembers his wife, Joanne, as a healthy 18-year-old with long brown hair and a '61 Chevy. They met through a social group at a Presbyterian church. They got married and had two children.

These days, he trims and curls Joanne's hair, because she no longer is able to do it herself. He brushes her teeth. He helps her dress. He cooks, cleans and drives her in a specially equipped van to the gym, where she battles the debilitating effects of two strokes. "If I was the ill person, I'm sure she would be doing this for me," said Wolf, 65, who retired five years ago as a printing company executive to care for his wife. "She wouldn't just put me in a nursing home and pack me away."

Joanne, 61, whose left side has recovered more than her right, is listening. "I'd be lost without him," she said. "He's my right-hand man."

The view that dutiful daughters and nurturing wives dominate the ranks of society's caregivers is out of date, health-care experts say. Both sexes, it turns out, are playing a crucial role -- and at significant personal cost -- in providing hands-on care to ailing relatives. Their efforts have emerged as a foundation of the larger U.S. health-care system, helping family members survive at home and perhaps prolonging their lives.

Among the almost 16 million family helpers who also hold full-time jobs outside the home, for example, men outnumber women 52 percent to 48 percent, according to a study this year by the MetLife Mature Market Institute and the National Alliance for Caregiving.

"The public perception is that women do all the care-giving. It's totally not true," said Peter S. Arno of the Montefiore Medical Center and Albert Einstein College of Medicine in New York. Overall, about 30 million family helpers are giving care 20 hours a week, with men providing more than 40 percent, Arno said, including help with eating, dressing, bathing and using the bathroom.

Male and female family members both can pay a price for their devotion. Risks escalate for illness and depression. Efforts to balance demands of care and career can be stressful and sometimes futile.

Anecdotally, however, some wonder if men at times pay their own peculiar price, particularly those who labor in isolation and bottle up their frustrations.

Betty J. Kramer, co-editor of Men as Caregivers and a professor of social work at the University of Wisconsin in Madison, recalled her experience guiding the male helpers.

"In one support group, two men had strokes and one had a heart attack," she said. In another case, a man was having anxiety attacks, she recalled. On further investigation, it turned out the attacks were prompted by going to the grocery store: "He'd never shopped before," she said.

For the baby boom generation, care decisions are becoming an increasingly important part of life. Already, boomers are the major providers of family help, most commonly assisting a parent who is battling conditions including Alzheimer's, stroke, Parkinson's disease, and multiple sclerosis.

Hollis-Eden Pharmaceuticals Presents Additional Positive Data with Drug Candidate HE3286 in Model of Rheumatoid Arthritis

Novel Steroid’s Anti-Inflammatory Activity Linked to Regulation of NF-kappaB and Increase of Treg Cells

SAN DIEGO--(BUSINESS WIRE)--Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) is presenting new data this week on an experimental drug candidate, HE3286, an orally active novel synthetic steroid hormone. Highlights from the presentation include findings demonstrating HE3286 had a dramatic benefit in a rodent model of rheumatoid arthritis. In a collagen-induced arthritis model (CIA), HE3286, when compared to placebo, significantly reduced the severity of disease and decreased disease over the course of the study. Moreover, histological analysis of joint tissue conducted at the end of the study indicated a marked reduction of tissue damage in the HE3286-treated animals compared to placebo. The findings are being presented this week in a series of oral presentations at the Fifth International Congress on Autoimmune Diseases being held in Sorrento, Italy.

The Company also is presenting further in vivo and in vitro data elucidating potential mechanisms of action for HE3286 that include regulation of NF-kappaB and increasing the production of regulatory T cells (Treg cells). NF-kappaB is a well-known transcription regulator that controls the production of inflammatory cytokines such as TNF-alpha and Interferon-gamma. Treg cells are referred to in the scientific literature as the peacekeepers of the body. Their role is to keep the immune system from attacking the body itself. Recent studies of Treg cells indicate that they may play a broader role than simply preventing autoimmune conditions. The medical literature is now suggesting that the manipulations of these cells could offer new treatments for conditions ranging from diabetes to organ rejection. At a previous scientific meeting the Company presented preclinical data demonstrating HE3286 improved glucose tolerance in a model of early insulin resistant type-II diabetes. The benefits in this model of diabetes were also believed to be attributable to the regulation of the NF-kappaB pathway and the increase in Treg cells.

Additional preclinical data presented at the conference demonstrate that HE3286 avoided unwanted side effects of immune suppression when compared to dexamethasone in well-established animal models. In a separate presentation, the Company also showed data suggesting that a newly identified subclass of compounds may potentially provide benefit to patients with various other autoimmune diseases, including multiple sclerosis. Preliminary studies suggest these compounds provided benefit in the SJL female mouse model of EAE, a widely used animal model of multiple sclerosis. Moreover, these compounds are highly potent at reducing inflammation in mouse models of LPS induced shock, regulating both NF-kappaB activation and levels of pro-inflammatory cytokines such as TNF-alpha.

“What was striking about these findings in the CIA animal model,” said Dr. Halina Offner, Professor of Neurology at Oregon Health Science University, who conducted the work, “is that HE3286 not only limited the severity of disease, but based on histology it also appeared to help repair the tissue damage in the joints of the mice. This is a remarkable and extremely intriguing observation.”

“This scientific meeting on autoimmune diseases represents a great opportunity for our scientists to take center stage at a major international conference to present data on our hormonal signaling technology platform drug candidates,” said Richard B. Hollis, Chairman and Chief Executive Officer of Hollis-Eden Pharmaceuticals. “Specifically, our drug candidate HE3286 has now been identified in several animal models as an exciting compound which could provide a new, clinically relevant breakthrough treatment in several indications, including rheumatoid arthritis, diabetes and inflammatory conditions of the lung. The observation that HE3286 treatment appeared to facilitate restoration of a damaged joint in the CIA model is particularly important as it is yet another piece of experimental evidence suggesting the potential usefulness of this class of compounds in regenerative medicine. The observed ability, in these preclinical models, of immune regulating hormones to have potent anti-inflammatory properties without side effects such as immune suppression and bone loss commonly associated with corticosteroids, provides the potential opportunity to use these compounds in a broad array of inflammatory conditions.”

About Hollis-Eden

Hollis-Eden Pharmaceuticals, Inc. is developing a proprietary new class of small molecule compounds that are metabolites or synthetic analogs of adrenal steroid hormones. These compounds, designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging, have been demonstrated in humans to possess several properties with potential therapeutic benefit – they regulate innate and adaptive immunity, reduce nonproductive inflammation and stimulate cell proliferation. The Company’s lead product candidate, NEUMUNE® (HE2100), is entering late-stage development for the treatment of Acute Radiation Syndrome (ARS), a life-threatening condition resulting from exposure to high levels of radiation following a nuclear or radiological incident, and is being explored for use in combating healthcare-associated infections. Hollis-Eden also is profiling optimized second-generation compounds for potential clinical development in a broad spectrum of therapeutic categories including hematology, metabolic disorders, autoimmune disorders, pulmonary diseases, oncology and infectious diseases. For more information on Hollis-Eden, visit the Company's website at www.holliseden.com.

This press release contains forward-looking statements within the meaning of the federal securities laws concerning, among other things, the potential and prospects of the Company's drug discovery program and its drug candidates. Any statements included in this press release that are not a description of historical facts are forward-looking statements that involve risks, uncertainties, assumptions and other factors which, if they do not materialize or prove correct, could cause the Company's actual results to differ materially from historical results or those expressed or implied by such forward-looking statements. Such statements are subject to certain risks and uncertainties inherent in the Company’s business, including, but not limited to: the ability to complete preclinical and clinical trials successfully and within specified timelines, if at all; the ability to obtain regulatory approval for NEUMUNE under the U.S. Food and Drug Administration Animal Efficacy Rule, even if shown to be effective in preclinical studies; the ability to receive any stockpiling orders for NEUMUNE from the U.S. federal, state and foreign governments or agencies, even if approved by regulatory authorities; the Company's future capital needs; the Company's ability to obtain additional funding; the ability of the Company to protect its intellectual property rights and to not infringe the intellectual property rights of others; the development of competitive products by other companies; and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Except as required by law, the Company undertakes no obligation to update or revise the information contained in this press release as a result of new information, future events or circumstances arising after the date of this press release.

Contacts
Hollis-Eden Pharmaceuticals
Dan Burgess or Scott Rieger, 858-587-9333

Amyloid-busting compound to start trials in Alzheimer’s

By Mike Nagle

28/11/2006 - US drug developer Samaritan Pharmaceuticals has filed a patent for a new drug that could treat a wide range of neurodegenerative disorders, including Alzheimer’s disease, by clearing out amyloid plaques in the brain.

The compound, called caprospinol (SP 233), is remarkable because it appears to not only block the formation of amyloid, thought to contribute to the nerve damage seen in Alzheimers patients, but also cause deposits already present in the brain to disappear.
Alzheimer's is an incurable, progressive brain disorder that causes dementia. Current treatments work to slow down the progress of the disease by boosting neurotransmitter levels in neurons, but it has not been possible to reverse any damage already done by the disease. Experimental strategies to treat the disease include gene therapy but as yet, are not employed clinically. Therefore, there is a pressing need for the development of new treatments.

The managing director of Samaritan Pharmaceuticals, Europe, Dr Christos Dakas, told DrugResearcher.com that aside from its potential in Alzheimer's, disease, ”our scientists believe that it [SP-233] could be effective in any disease that involves neurodegeneration. But it is not something we'll be pursuing at this stage.”

Other neurodegenerative diseases include Huntington disease, multiple sclerosis and Parkinson's disease.

The main constituent of amyloid plaques, amyloid-beta protein, accumulates at abnormal levels in the brain of Alzheimer's sufferers. The protein is toxic to mitochondria found in cells and ultimately causes nerve cell death. This in turn, causes the symptoms of the disease, including loss of memory, an inability to learn, make judgments and perform day-to-day tasks. Caprospinol has been developed to protect mitochondria functions against the effects of amyloid-beta. It does this by binding to amyloid-beta and preventing it entering neurons.

Dr Dakas said: “We are in the process of initialising a Phase I maximum dose and safety study.”

The study should be completed in the first quarter of 2007 and Dr Dakas hopes that if everything continues to progress well, the drug could be available in two to three years.

He added: “We have three more products in development in the Alzhemier's disease program. At this stage, SP-233 is the most advanced.”

Several other drugs designed to taget amyloid formation are in development. US Pharmaceutical company Elan, in collaboration with Wyeth, New Jersey, have developed a drug aimed at inducing an immune resonse designed to clear beta amyloid. The drug, ACC-001 is currently in Phase I clinical trials.

Frence based ExonHit Therapeutics are developing a drug that reduces amyloid plaque build-up through the production of a related blood protein. EHT 0202 has completed a Phase I clinical trial and is currently being assessed in Phase Ib trials.

A further study has shown that a drug previously approved for treatment of several immune disorders can also benefit patients with mild to moderate Alzheimer's. Weill Medical College of Cornell University, New York, have demonstrated that Intravenous Immunoglobulin (IVIg), a purified mixture of human antibodies, can be used to remove amyloid plaques from the brain. The antibiotics also appear to block the toxic effects of amyloid-beta.

MultiCell Technologies Obtains Patent Protection in Several European Countries for Treatment of Autoimmune Diseases

SAN DIEGO--(BUSINESS WIRE)--Nov 29, 2006 - MultiCell Technologies, Inc. (OTCBB:MCET), developing first-in-class drugs based on advanced immune system modulation and other proprietary technologies, today announced it has obtained patent protection for their latest issued European patent in several countries, including France, Germany, Switzerland, U.K., Ireland, Belgium, Luxembourg and Monaco. This patent covers next generation technology from MCET, targeting multibillion-dollar medical marketplace segments, including a range of serious autoimmune disorders such as type-1 diabetes and multiple sclerosis.

The patent, which was issued last month by the European Patent Office, is a milestone validation of the Company's business strategy to obtain broad, worldwide protection of its advanced immune modulation technologies and intellectual property. The patent has helped push the Company's IP portfolio past the 70 issued or pending patent threshold.

MultiCell is leveraging its breakthrough technology platforms to develop a new generation of therapeutic candidates which stimulate or suppress the immune system to treat such conditions as multiple sclerosis, type-1 diabetes, virally caused cancers, and infectious disease.

"From its inception, MultiCell has been committed to competing on the international stage," said Dr. Stephen Chang, Chief Executive Officer of MultiCell Technologies. "We believe the issuance of the patent by several European nations further validates our technology and continues to build value for our shareholders."

The patent, "Compositions for Treating Autoimmune Disease", leverages MultiCell's proprietary platform technologies for modulating the immune response to treat a range of serious diseases.

The newly issued patent is related to compositions for the effective presentation of immunosuppressive factors that are useful for the treatment of various disorders. The Company's technology platforms include Toll-like Receptor signaling and T-cell targeting to modulate both the innate and adaptive immune systems. These technologies enable the creation of advanced drug candidates that stimulate or suppress the immune system via disease-specific targeting.

About MultiCell Technologies, Inc.

MultiCell Technologies, Inc. is an integrated biopharmaceutical company committed to the development of breakthrough therapeutics based on a portfolio of therapeutic candidates and patented drug development technology. MultiCell's drug development program is focused on modulation of the immune system. MultiCell's therapeutic pipeline includes drug candidates some of which are in various advanced stages of human clinical trials. These therapies include:

-- MCT-125 for the treatment of chronic fatigue in MS patients. MCT-125 completed a Phase II clinical trial and demonstrated significant efficacy in reducing chronic fatigue in MS patients. There is no drug specifically approved for the treatment of chronic fatigue in MS patients anywhere in the world.

-- MCT-175 for the treatment of relapsing-remitting MS. MCT-175, in preclinical development for the treatment of relapsing-remitting MS, targets disease specific autoaggressive T-cells that destroy the myelin sheath of nerve cells. MCT-175 successfully ameliorated the disease in animal models.

-- MCT-275 for the treatment of type-1 diabetes. MCT-275, in preclinical development, targets disease-specific autoaggressive T-cells that destroy insulin producing cells in the pancreas. MCT-275 completely reversed the type-1 diabetic phenotype and prolonged life in animal models.

-- MCT-465 in an adjuvant therapy for the treatment of virus infection and cancer. MCT-465 in preclinical studies successfully reduced pulmonary influenza virus levels 1,000-fold in animal models, and has demonstrated effectiveness in reducing virus levels of HIV and HCV in animal models. MCT-465 in preclinical studies successfully eliminated certain types of tumors in animal models.

The Company also holds unique cell-based technology for use in drug discovery screening applications, and is a leading producer of the cell lines needed by the biotechnology industry to develop new drugs and therapeutics.

For more information about MultiCell Technologies, please visit http://www.MultiCelltech.com. For investor information about MultiCell, please visit http://www.trilogy-capital.com/tcp/multicell. For current stock price quotes and news, visit http://www.trilogy-capital.com/tcp/multicell/quote.html. To view the Company's Investor Fact Sheet, visit http://www.trilogy-capital.com/tcp/multicell/factsheet.html. To listen to an archived investor conference call, visit http://www.trilogy-capital.com/tcp/multicell/conference.html.

Forward-Looking Statements

Any statements in this press release about MultiCell's expectations, beliefs, plans, objectives, assumptions or future events or performance are not historical facts and are forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). These statements are often, but not always, made through the use of words or phrases such as "believe," "will," "expect," "anticipate," "estimate," "intend," "plan," "forecast," "could" and "would." Examples of such forward-looking statements include statements regarding developing products that address unmet medical needs. MultiCell bases these forward-looking statements on current expectations about future events. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, levels of activity, performance or achievements to differ materially from those expressed or implied by any forward-looking statement. Some of the risks, uncertainties and assumptions that could cause actual results to differ materially from estimates or projections in the forward-looking statement include, but are not limited to, the risk that we might not achieve our anticipated clinical development milestones, receive regulatory approval, or successfully commercialize our lead drug candidates as expected, the market for our products will not grow as expected, and the risk that our products will not achieve expectations. For additional information about risks and uncertainties MultiCell faces, see documents MultiCell files with the SEC, including MultiCell's report on Form 10-KSB for the fiscal year ended November 30, 2005, and all our quarterly and other periodic SEC filings. MultiCell claims the protection of the safe harbor for forward-looking statements under the Act and each assume no obligation and expressly disclaim any duty to update any forward-looking statement to reflect events or circumstances after the date of this news release or to reflect the occurrence of subsequent events.

Contact

MultiCell Technologies, Inc.
Dr. Stephen Chang, 619-743-3806
MCETInvestor@MultiCelltech.com

Stem Cell Therapy International Reports the Successful Treatment of a Stroke Patient With Their Proprietary Stem Cell Transplantation Therapy

TAMPA, FL -- (MARKET WIRE) -- November 29, 2006 -- Stem Cell Therapy International, Inc. (PINKSHEETS: SCII), a company in the field of research and development of stem cell transplantation therapy and regenerative medicine, announced today the successful treatment of a stroke patient from the United States with its stem cell transplantation therapy protocol conducted at one of their affiliate clinics in Kiev, Ukraine.

Dr. Rich James, 50, a practicing Chiropractor in New York City, whose left arm and left leg were paralyzed as a result of a stroke that he suffered in February of 2006, had undergone traditional medical treatment available for stroke survivors here in the US with only limited results.

Dr. James said, "I realized that I could live for another thirty years. I did not want to live with the crippling effects of my stroke. Physical therapy and occupational therapy could only do so much in helping me get the function back on my paralyzed side."

Dr. James, after his stroke, became a member of the on-line global stroke survivor support community StrokeNetwork.org and was able to contact Stem Cell Therapy International from the information posted by SCTI on their website with the permission of Steve Mallory, the founder, President and CEO of the StrokeNetwork.

Steve Mallory stated his reasons for creating the StrokeNetwork: "I founded the on-line stroke support network so that we are available to everybody around the world on a 24/7 basis. Our mission is to provide on-line stroke support to all adult stroke survivors and also to stroke caregivers."

Mr. Mallory goes on to say, "In the future, I foresee stem cell transplantation therapy being used by stroke survivors to regain physical improvements on some of the deficits caused by their stroke. The resulting effects will definitely improve their 'quality of life.'"

Calvin Cao, CEO of Stem Cell Therapy International, said, "After his stroke Dr. James was in a wheelchair but could walk short distances with the aid of an AFO and a quad cane. He traveled to our affiliate clinic in Kiev and received stem cell transplantation therapy as well as physical and massage therapy. At six weeks post treatment, Dr. James can walk without any aids and at four months post treatment he is now able to take the NY subway on his own to get around."

Mr. Cao said, "Dr. James has been posting a blog journal about his experience in having the stroke and the support of the members of the StrokeNetwork and Stem Cell Therapy International. We invite everyone to log on to our website at www.scticorp.com, click on the 'In The Spotlight' section and read the comments from Dr. James about his continuing recovery from his stroke after stem cell transplantation therapy."

Stem cell transplantation therapy is a field of medicine, which uses techniques and technologies that rely on replacing diseased, damaged or dysfunctional cells with healthy, functioning ones. The SCTI proprietary therapy is similar to the process of organ transplantation, only the treatment consists of the transplantation of stem cells into the body rather than entire organs, thus eliminating any chance of rejection or the need for expensive and potentially dangerous immunosuppression drug therapy. These new techniques are being applied to finding a cure for a wide range of human disorders in SCTI affiliated medical facilities outside of the United States.

With the enactment of Proposition 71 in California in November 2004, a fund of $3 billion was created to fund stem cell research. Since then a number of other states such as New Jersey, Massachusetts, Connecticut, Illinois and Wisconsin, have allocated funds for additional stem cell research in the US.

About Stem Cell Therapy International (SCTI)

Stem Cell Therapy International, Inc. is engaged in the field of regenerative medicine. This includes ongoing research, development and the treatment of patients with stem cell transplantation therapy. SCTI manufactures the stem cell biological solutions that is currently being used in the treatment of patients suffering from degenerative disorders of the human body such as Alzheimer's, Parkinson's Disease, ALS, leukemia, muscular dystrophy, multiple sclerosis, arthritis, spinal cord injuries, brain injury, stroke, heart disease, liver and retinal disease, diabetes as well as certain types of cancer. The Company has established license agreements with highly specialized, professional medical treatment facilities around the world in locations where stem cell transplantation therapy is approved by the appropriate local government agencies. SCTI plans to provide these stem cell biological solutions to universities, institutes and privately funded laboratory facilities in the United States for research purposes and clinical trials. Its products, which are available now for treatment, include various stem cell biological solutions which contain human stem cells, low-molecular proteins and human growth factor hormones.

Forward-Looking Statements

This report includes "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934. The information in this news release includes certain forward-looking statements that are based upon assumptions that in the future may prove not to have been accurate and are subject to significant risks and uncertainties, including statements as to the future performance of the company. Although the company believes that the expectations reflected in its forward-looking statements are reasonable, it can give no assurance that such expectations or any of its forward-looking statements will prove to be correct. Factors that could cause results to differ include, but are not limited to, successful performance of internal plans, product development acceptance, and the impact of competitive services and pricing and general economic risks and uncertainties.


For more information, please contact:

Stem Cell Therapy International
Investor Relations
Calvin C. Cao
Chairman and CEO
T: 813-600-4088
E: calvin@scticorp.com

Stem Cell Therapy International
Media Relations
Peter K. Sidorenko
Chief Operating Officer
T: 813-600-0088
E: peter@scticorp.com

SOURCE: Stem Cell Therapy International, Inc.

Low impact aerobic exercise reduces fatigue in auto-immune conditions says multi-study review

Contact: Annette Whibley
wizard.media@virgin.net
Blackwell Publishing Ltd.


Low impact aerobic exercise, such as walking and cycling, can effectively reduce fatigue in adults with chronic auto-immune conditions, according to a research review in the latest issue of the UK-based Journal of Advanced Nursing.

A team led by nurse researcher Dr Jane Neill from Flinders University in Adelaide, examined 162 research studies published between 1987 and 2006, analysing 36 in detail.

They discovered that there was evidence that people with conditions like multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus could benefit from exercise that gradually increased in intensity, duration and frequency.

“Fatigue is a major symptom in all three conditions and can cause a range of physical, psychological and social problems” says Dr Neill.

“Our review showed that aerobic exercise can significantly reduce fatigue and that some behavioural, nutritional and physiological interventions are also very effective.”

Studies reviewed by the team tested 38 interventions on more than 1,700 patients. 24 resulted in statistically reduced fatigue or increased vitality levels.

The effective aerobic exercise programmes lasted an average of 12 weeks, with participants exercising for 30 to 60 minutes, three times a week.

Group interventions involved supervised exercise classes, including warm up, low impact aerobic activity and strengthening or stretching exercises before cool down.

Home-based programmes made use of exercise bicycles, walking, cycling, jogging or swimming.

“There is good evidence that people experiencing fatigue from chronic auto-immune conditions can benefit from a range of non-medicinal interventions” concludes Dr Neill.

“Other effective strategies, apart from aerobic exercise, include health education and cognitive behavioural therapy.

“Cooling techniques and nutritional supplements such as acetyl-L-carnitine and fish oil showed a number of benefits, but need to be looked at in more detail.”

The authors suggest electro-magnetic field devices also warrant further investigation, due to promising results.

But they add that low-cost, low technology interventions that promote self-management of fatigue are probably more appropriate and feasible than those requiring specialised equipment or professional expertise.

They stress that any exercise programmes must be suitable for each individual and take account of issues that affect how people manage their conditions, like reduced mobility, pain, nausea and stress.

“Healthcare professionals should ask people about their fatigue and assess each person’s symptoms” adds Dr Neill. “People with fatigue should be encouraged to design their own exercise routines based on awareness of their individual fatigue patterns and daily priorities, while group activities must take account of the changing nature of fatigue over time.”

Previous research suggests that 70 per cent of people with multiple sclerosis suffer daily fatigue, 57 per cent of people with rheumatoid arthritis experience fatigue and 81 per cent of those with system lupus erythematosus find fatigue moderately to severely disabling.

“Any measures that can reduce people’s fatigue and improve their quality of life are to be welcomed. Our review shows that some interventions have great potential, particularly in the short term, but that more research is needed to measure their long-term effectiveness” says Dr Neill.

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Notes to editors

Effectiveness of non-pharmacological interventions for fatigue in adults with multiple sclerosis, rheumatoid arthritis or systemic lupus erythematosus: a systematic review. Neill J, Belan I and Ried K. Journal of Advanced Nursing. Volume 56.6, pages 617-635.

Journal of Advanced Nursing, which is celebrating its 30th anniversary in 2006, is read by experienced nurses, midwives, health visitors and advanced nursing students in over 80 countries. It informs, educates, explores, debates and challenges the foundations of nursing health care knowledge and practice worldwide. Edited by Professor Alison Tierney, it is published 24 times a year by Blackwell Publishing Ltd, part of the international Blackwell Publishing group.
www.journalofadvancednursing.com

Novartis Highlights Strong R&D Pipeline, Plans for Multiple New Product Launches and Novel Projects Moving Into Late-stage Trials

One of the strongest pipelines with 138 projects in pharmaceutical development, focusing on areas of high unmet medical needs.

Exforge[1] and Tekturna[1] (US/EU, hypertension), Galvus[1] (US/EU, diabetes), Tasigna[1] (US/EU, cancer) and Lucentis (EU, eye disease) all submitted for major approvals.

Accelerated US and European Union submissions completed for Tasigna and Aclasta/Reclast[1] (osteoporosis) in 2006 ahead of plans for next year

Late-stage compounds moving into pivotal trials - FTY720 (multiple sclerosis), QAB149 (COPD/asthma), AGO178 (depression), ABF656 (hepatitis C), RAD001 (cancer) and SOM230 (Cushing's disease)

Among vaccine portfolio highlights, H5N1 pre-pandemic influenza vaccine shows positive results in Phase II volunteer trial and EU submission completed

LONDON, November 28, 2006 - Novartis unveiled today new data on its promising pipeline amid plans for multiple new product approvals and launches over the next two years. Many of these anticipated approvals are for potentially best-in-class medicines that would advance treatment standards for patients with hypertension, diabetes, cancer and other diseases.


Novartis highlighted progress throughout its pipeline, particularly the advance of pharmaceutical compounds to pivotal trials before regulatory submission as well as the development portfolio in the newly created Vaccines and Diagnostics division.

The following compounds are moving into pivotal late-stage trials: FTY720 (fingolimod) for multiple sclerosis, QAB149 (indacaterol) for COPD and asthma, AG0178 (agomelatine) for depression and ABF656 (Albuferon(TM)) for hepatitis C as well as RAD001 (everolimus) for cancer and SOM230 (pasireotide) for Cushing's disease.

"I am pleased that our sustained focus on innovation and drive to address unmet medical needs have enabled us to further strengthen our pipeline and file several new drugs for regulatory review over the past 12 months," said Dr. Daniel Vasella, Chairman and CEO of Novartis.

"Over the next two years we will launch several innovative medicines and continue to invest aggressively in discovery research and development activities and complement our own skills and technologies through attractive collaborations," Dr. Vasella said.

In total, Novartis now has 138 projects in pharmaceutical clinical development. Of these, 94 projects are in confirmatory development (Phase IIb, Phase III or registration with regulatory authorities). A total of 50 are new molecular entities (NMEs), while 88 are life-cycle management projects involving new indications or formulations.[2] More than 20 projects have been added to the pipeline during 2006. Key R&D areas are cardiovascular/metabolic conditions, oncology and neuroscience as well as respiratory and infectious diseases.

Novartis has completed many submissions in 2006 to regulatory authorities for new compounds as well as new indications for medicines already available to patients.

The US and EU regulatory submissions were accelerated and completed ahead of schedule in 2006 for two compounds: Tasigna (nilotinib) as a new treatment option for patients with resistance and/or intolerance to treatment with Gleevec/Glivec for certain forms of chronic myeloid leukemia (CML), and also for Aclasta/Reclast (zoledronic acid) as a once-yearly bisphosphonate infusion for women with postmenopausal osteoporosis.

US regulatory decisions are also expected for Tekturna (aliskiren), a renin inhibitor for hypertension, and Exforge (valsartan and amlodipine), a single-tablet combination of the two most prescribed hypertension medicines in their respective classes.

Awaiting European Commission approval are Exforge and Lucentis, a new treatment option for patients with the "wet" form of age-related macular degeneration (AMD), after both compounds received positive recommendations in November from the Committee for Medicinal Products for Human Use (CHMP). The Commission generally follows the recommendations of the CHMP and delivers a final decision within two to three months.

A US regulatory decision is also expected in the first half of 2007 for Galvus (vildagliptin) as a once-daily oral treatment for patients with type 2 diabetes. The US Food and Drug Administration (FDA) extended the review period for Galvus by three months from November 2006 after recently available clinical data were submitted to support the proposed dosing and indications as well as complement earlier data on the risk/benefit profile.

Sustained leadership in hypertension Approvals of Exforge and Tekturna would further strengthen the leadership of Novartis in offering a broad range of treatments for patients with hypertension, complementing the in-market brands Diovan and Lotrel.

High blood pressure - and its consequences - is the world's No. 1 killer, estimated by the American Heart Association to affect one in four adults, or around one billion people globally. Despite extensive use of current therapies, about 70% of all people with high blood pressure do not reach target blood pressure levels. Many require two or more medicines to gain control.

Exforge is the first medicine to combine the angiotensin receptor blocker (ARB) valsartan (Diovan) and the calcium channel blocker (CCB) amlodipine besylate. More than 80% of Exforge patients in studies reached their recommended blood pressure goals and also experienced a lower rate of peripheral edema (swelling of the ankles) compared to those taking amlodipine alone.

Tekturna, which was developed in collaboration with Speedel, has shown a strong efficacy profile in hypertension patients. New data presented at the event showed Tekturna demonstrated a statistically significant (p=0.0004) reduction in blood pressure compared to a diuretic (hydrochlorothiazide), while results from this 12-week trial also showed strong efficacy in combination with the same diuretic in obese patients. Tekturna has shown placebo-like safety at the proposed maximum once-daily dose of 300 mg.

In another new study, the combination of Tekturna and Diovan showed a significant additive reduction in blood pressure compared to Diovan alone, with a drop in systolic blood pressure of about 17 mm Hg compared to about 13 mm Hg for either Tekturna or Diovan alone.

Additional data support efficacy and safety of Galvus Novartis is confident in the efficacy and safety of Galvus and in obtaining US approval for this once-daily oral treatment for patients with type 2 diabetes. Results from recently completed clinical trials are being submitted to the FDA involving an additional 1,000 patient-years of treatment experience.

These data include results from short- and long-term studies for periods of up to two years, both as a monotherapy or in combination with other anti-diabetes medicines. They further support the proposed dosing regimen and indications as well as complement the risk/benefit profile of Galvus. In particular, they provide further evidence confirming data submitted earlier to the FDA showing that skin findings identified in a single species during a preclinical animal study have not been seen in clinical studies with type 2 diabetes patients.

New data presented at the event again confirmed the once-daily efficacy of Galvus, while pooled monotherapy data showed a 1.1% reduction in HbA1c (a measure of average blood sugar levels) in initial use by type 2 diabetes patients starting treatment. The results of a 104-week trial continued to show the sustained reduction of 1% in HbA1c seen at 52 weeks, but narrowly missed the primary endpoint of non-inferiority versus metformin. However, Galvus was better tolerated than metformin, particularly with a superior gastrointestinal tolerability profile.

Vaccines pipeline supports existing franchises and explores new fields Novartis has assembled a strong pipeline of investigational human vaccine projects following the acquisition of Chiron in April 2006, focusing on supporting existing franchises in influenza, meningitis and travel vaccines while exploring new disease areas.

Among new data presented at the event were the positive results of a Phase II trial involving 500 volunteers inoculated with an adjuvanted H5N1 pre-pandemic vaccine. Results showed that various levels mandated by European regulators for seroprotection, seroconversion increase and mean geometric increase of H5N1-specific antibodies were achieved. Novartis announced today that this vaccine has been submitted for European approval for use as a pre-pandemic vaccine to boost the immune system's ability to defend against infections from an H5N1 strain.

The OptaFlu seasonal influenza vaccine, which is based on novel cell culture technology instead of traditional egg-based production, showed in pivotal Phase III data that it was highly capable of producing an immune response ("immunogenic"), at least as strong as the egg-based vaccine Agrippal® for each of the three influenza strains studied. It was also well tolerated, showing no meaningful differences in the safety profile compared to traditional egg-based vaccines. The EU submission was completed in 2006, while the US submission is planned for 2008. Novartis also announced progress in the development of its conjugate quadrivalent MenACWY vaccine against the A, C, W135 and Y serogroups of Neisseria meningitides, important causes of bacterial meningitis. This devastating disease is estimated to strike about three to five of 100,000 people per year - particularly infants and children. Phase III trials involving 13,000 people started in April 2006, targeting regulatory submission for use in infants, adolescents and adults.

A vaccine for the B serogroup of meningitis B, for which there is currently no effective vaccine, is also in Phase II studies to identify dosing in adolescents, with data expected by the end of 2007.

Productive innovation filling the early-stage pipeline New discovery approaches at the Novartis Institutes for BioMedical Research (NIBR), which was created four years ago to enhance the Group's long tradition of drug discovery, are contributing novel compounds to clinical development.

The number of new molecular entities in the NIBR portfolio has increased to more than 70 in 2006 (compared to 55 in 2004), driven in part by new target discovery, enhanced structural biology, and rapid growth in the number of biological therapeutic drug candidates. These include antibodies, which now constitute about 25% of the NIBR portfolio.

Selected Pipeline Event highlights Among projects highlighted at the event were the following:

Aclasta/Reclast (zoledronic acid), a once-yearly bisphosphonate treatment for women with postmenopausal osteoporosis, has been submitted for US and EU approval earlier than planned. This was based on pivotal Phase III data showing that patients taking Aclasta/Reclast experienced a highly significant 70% risk reduction in new spine fractures (p<0.0001) and a 41% risk reduction in hip fractures (p=0.0024) over three years compared to placebo. This met the study's two primary endpoints. Additionally, all secondary endpoints were met, including risk reduction in clinical spine and non-spine fractures. This high level of efficacy was sustained in the second and third years of the study, while Aclasta/Reclast was generally safe and well tolerated.

AEB071, a first-in-class protein kinase C (PKC) inhibitor, is aiming to become the first oral treatment that inhibits T-cell activation since the introduction of calcineurin inhibitors. T-cell activation is an early step in autoimmune diseases such as psoriasis and is also essential for the rejection of transplanted organs. AEB071 blocks a pathway critical to T-cell activation and has shown promise in organ transplantation as well as in autoimmune disorders. It has shown improvements in psoriatic skin lesions in an early proof-of-concept study and recently started Phase II clinical trials for organ transplantation (prevention of graft rejection). Submission is planned for after 2010.

AGO178 (agomelatine), seeking to become a new once-daily treatment for patients with major depression, is set to begin Phase III trials in the US by the end of 2006. The US rights to this compound were acquired in March 2006 from Servier. AGO178 has shown efficacy comparable to current standard therapies such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) while offering improved tolerability, including a low propensity to cause sexual dysfunction and weight gain as well as an improvement in the quality of sleep. US submission is planned for 2008.

ABF656 (Albuferon(TM)) (albumin interferon alpha-2b), a novel long-acting interferon targeting hepatitis C, is entering Phase III trials. Interim results from Phase II trials, in which treatment-naïve patients received Albuferon in combination with ribavirin, showed it has the potential for an improved efficacy and tolerability profile with the need for fewer injections compared to pegylated interferon, the current standard of care. Hepatitis C is a liver disease caused by a chronic viral infection estimated to affect more than 170 million patients worldwide. Novartis and Human Genome Sciences will co-promote Albuferon in the US, while Novartis will have exclusive rights in the rest of the world. The first regulatory submission is planned for 2009.

EPO906 (patupilone), a novel tubulin polymerizing compound known as an epothilone, has experienced unexpectedly slow patient accrual for a registration trial in ovarian cancer that was started in 2005, delaying submission. A protocol amendment has been made and the number of centers expanded.

Exelon Patch (rivastigmine transdermal patch) has been submitted for US and EU approval as a once-daily treatment for patients with Alzheimer's disease. The IDEAL study of about 1,200 patients showed that Exelon Patch provided benefits across a wide range of symptoms and that the target dose was well tolerated. Transdermal patches are designed to provide controlled, continuous delivery of a medicine through the skin, meaning patients could potentially avoid gastrointestinal problems associated with certain oral medicines. Patients using Exelon Patch had improved memory and thinking, and were also better able to perform everyday activities than those on placebo.

Exjade (deferasirox) has been launched in the US and Europe as the first and only once-daily oral iron chelator for chronic iron overload in transfusion-related conditions. It is now being studied in patients with non-transfusional-related iron overload. Phase I/II safety and efficacy studies are enrolling patients, with the first data expected in 2008.

FTY720 (fingolimod), seeking to become the first oral disease-modifying treatment for patients with relapsing multiple sclerosis (MS), is being studied in a Phase III program underway with the goal of enrolling more than 3,000 patients worldwide. A two-year placebo-controlled program (FREEDOMS) is measuring reductions in the frequency of relapses and disability progression in MS patients. A one-year trial (TRANFORMS) started in May 2006 comparing FTY720 with interferon beta-1a (Avonex®). Two-year data from the extension of a Phase II trial showed sustained benefits, indicating that FTY720 could provide an important new option for the estimated 2.5 million people worldwide suffering from this disabling neurological disease. Submission remains on track for 2009.

LBH589, a highly potent deacetylase inhibitor shown to impede multiple pathways implicated in cancer, is planned to start a pivotal Phase II registration study by the end of 2006 in patients with cutaneous T-cell lymphoma. Submission is planned for the second half of 2008 for this compound. Novartis intends to explore the use of this compound in other challenging malignancies.

Mycograb (antifungal) and Aurograb (antibacterial), acquired through the purchase of NeuTec in mid-2006, strengthened the presence of Novartis in the fast-growing market for hospital anti-infectives that address life-threatening diseases. Mycograb in combination with amphotericin B has demonstrated superiority in terms of clinical cure rate and Candida-related mortality. Novartis announced in November 2006 that it plans to submit additional clarification to European regulators to support the approval of Mycograb after receiving a negative recommendation on the submission made by NeuTec in 2005. Submission in the US is planned for 2009. Aurograb is being developed as an add-on therapy to vancomycin in targeting serious staphylococcus aureus infections, including resistant strains. Novartis is considering trials with other antibacterials as an add-on therapy. US and EU submissions for Aurograb are planned for 2010.

Prexige (lumiracoxib) successfully completed the European Union's Mutual Recognition Procedure (MRP) in October, with all EU member states agreeing to issue approvals. European launches for this treatment for patients suffering from osteoarthritic pain of the knee and hip are planned to start in the first quarter of 2007. Prexige was also approved in Canada in early November. Resubmission for US approval is planned for 2007.

QAB149 (indacaterol), seeking to become the first once-daily long-acting beta-agonist with 24-hour bronchodilation and a fast onset of action, is being developed to treat respiratory diseases as a monotherapy and in combination with other medicines. A 52-week monotherapy Phase III trial began in the fourth quarter of 2006 in patients with chronic obstructive pulmonary disease (COPD), a condition often caused by smoking. The QMF149 program, which combines QAB149 with the once-daily inhaled corticosteroid mometasone (Asmanex®)[3], is set to begin trials in 2007 with plans for the first regulatory submission in 2010. A Phase III monotherapy trial for QAB149 in asthma patients is part of the QMF149 program. The new QVA149 program, also set to begin in 2007, will assess in COPD patients the potential of a once-daily fixed-dose combination of QAB149 and the once-daily inhaled long-acting muscarinic antagonist NVA237, which delivered positive efficacy and safety data in Phase II trials. This novel combination is expected to show superior bronchodilation compared to the individual compounds alone due to their complementary mechanisms of action.

RAD001 (everolimus), a novel oral inhibitor of the mTOR pathway considered a key target in oncology, has demonstrated broad clinical activity in multiple tumor types at well-tolerated and efficacious doses. A registration program is underway that includes the RADIANT-1 study in chemotherapy-refractory pancreatic islet cell tumors (pICT) and the RECORD-1 study in metastatic renal cell carcinoma. This program will be expanded in 2007 to include registration trials for refractory carcinoid tumors as well as first- and second-line pICT. RAD001 acts by directly inhibiting tumor cell growth as well as by inhibiting the formation of new blood vessels (angiogenesis). If the chemotherapy refractory pICT trial results are positive, the first submission could be as early as 2008.

SOM230 (pasireotide), a next-generation somatostatin analogue therapy, has completed Phase II studies in Cushing's disease, a rare disorder characterized by excessive excretion of the hormone cortisol from a pituitary adenoma (tumor), a condition for which there is no approved medical therapy. Registration studies are set to begin by year end. A registration trial in refractory carcinoid tumors is set to begin in the first quarter of 2007.

Tasigna (nilotinib, formerly AMN107) has been submitted for US and EU approval as a new option for patients with resistance and/or intolerance to treatment with Gleevec/Glivec for certain forms of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). A submission for this indication in Japan is expected by mid-2007. Interim Phase II results found that 46% of patients with CML resistant or intolerant to optimized Gleevec/Glivec therapy achieved a major cytogenic response with Tasigna after six months of treatment. Updated pivotal submission data will be presented at the American Society of Hematology meeting in December 2006. Both Tasigna and Gleevec/Glivec inhibit Bcr-Abl, the cause of Ph+ CML. Tasigna was specifically designed to be a more selective inhibitor of Bcr-Abl and its mutations. New registration studies are set to start in 2007 for Tasigna in gastrointestinal stromal tumors (GIST), patients with CML responding sub-optimally to other therapies and newly-diagnosed CML patients.

Zometa (zoledronic acid) is on track for EU submission in the 2007 first quarter for the treatment of bone loss associated with aromatase inhibitors, a condition known as AIBL. Latest data from the ZO-FAST and Z-FAST studies assessing the efficacy of Zometa in AIBL will be presented at the San Antonio Breast Cancer Symposium in December 2006.
Projects that have been terminated include XBD173 (generalized anxiety disorder) and AAE581 (osteoporosis), while LIC477 (bipolar disorder) has been delayed.

Disclaimer
This release contains certain forward-looking statements, relating to the Novartis Group's business, which can be identified by the use of forward-looking terminology such as "pipeline", "moving into", "promising", "plans", "anticipated", "anticipated", "will", "continue to", "expected", "awaiting", "generally follows . and delivers", "would further strengthen", "estimated", "targeting", "aiming", "planned", "set to", "potential", "seeking to", "goal", "could provide", "intends", "considering", "is being developed", "could be", "on track", or similar expressions, or by express or implied discussions regarding potential filings or marketing approvals, or potential future sales of candidate compounds vaccines, or potential new indications for existing products. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any existing or future regulatory filings will satisfy the FDA's and other health authorities' requirements regarding any one or more candidate compounds, vaccines, or new indications for existing products. Nor can there be any guarantees that such compounds, vaccines or new indications will be approved by any health authorities for sale in any market. Neither can there be any guarantee that any such compounds, vaccines or new indications will reach any particular level of sales. In particular, management's expectations regarding the approval and commercialization of the candidate compounds, vaccines and new indications could be affected by, among other things, unexpected clinical trial results, including additional analysis of existing clinical data, and new clinical data; unexpected regulatory actions or delays, or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; as well as the additional factors discussed in Novartis AG's Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

About Novartis
Novartis is a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 99,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

[1] Brand name awaiting approval by regulatory authorities. All product names appearing in italics are trademarks of Novartis Group Companies.

[2] Figures for life-cycle management projects have been adjusted to conform with industry benchmarking figures. However, no change has been made in the definition or method of reporting new molecular entities.

[3] In collaboration with Schering-Plough.

# # #

Media Relations

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Investor Relations

International Ruth Metzler-Arnold +41 61 324 7944 Katharina Ambühl +41 61 324 5316 Nafida Bendali +41 61 324 3514 Jason Hannon +41 61 324 2152 Richard Jarvis +41 61 324 4353 Silke Zentner +41 61 324 8612

North America Ronen Tamir +1 212 830 2433 Arun Nadiga +1 212 830 2444 Jill Pozarek +1 212 830 2445 Edwin Valeriano +1 212 830 2456


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Study Shows Pregabalin Effective in Difficult-to-Treat Nerve Pain

November 28, 2006 - 3:38 PM

SYDNEY, Australia, November 28/PRNewswire/ --


- Results Offer Hope to Patients With Excruciating Chronic Pain

Findings from a new study published today in the journal Neurology demonstrate that the oral medication pregabalin is significantly effective in relieving central neuropathic (nerve) pain and improves pain-related sleep disturbance and anxiety in patients with spinal cord injury. Conducted by researchers at the Pain Management Research Institute in Sydney, the study is the largest controlled clinical trial ever of patients with spinal cord injury who suffer from central neuropathic pain, a particularly persistent and severe pain condition.

Results from the study showed that patients using pregabalin (150-600 mg/day) experienced significant improvements in symptoms as early as the first week of treatment and those improvements were sustained throughout the study. Patients taking pregabalin experienced a significant reduction in the average intensity of their pain and significant improvements in pain-related sleep interference as well as a reduction in anxiety compared to those taking placebo.

"Historically it has been extremely difficult to manage patients with central neuropathic pain due to a lack of effective treatments and many people with spinal cord injury have excruciating pain," said Prof. Philip Siddall, lead investigator of the study and Clinical Associate Professor at the Pain Management Research Institute in Sydney. "The study demonstrates that pregabalin is an effective and well-tolerated therapy for treating a range of symptoms that can negatively impact overall quality of life. This study is an important step forward for clinicians trying to improve the lives of patients suffering from difficult-to-treat nerve pains."

Approximately two-thirds of patients with spinal cord injury often suffer from severe central neuropathic pain,[1],[2] which is caused by a lesion or dysfunction in the central nervous system.[3] Patients often describe the symptoms of their pain as burning, tingling, stabbing, shooting, pricking, scalding and freezing.[4],[5],[6] Chronic pain following spinal cord injury may limit a patient's ability to perform daily activities.[7] Consequently, quality of life may be impaired.[8] Central neuropathic pain can occur in patients with spinal cord injury, stroke, multiple sclerosis and neoplasia.

Pregabalin is believed to work by calming hyper-excited neurons or nerve cells which may be an underlying cause for various types of nerve pain.

Based on the results of this study, pregabalin recently became the only therapy to receive European regulatory approval in central neuropathic pain.


About the Study

The study, sponsored by pregabalin (Lyrica(R)) developer Pfizer Inc, was a multicentre, parallel-group, double-blind, randomised clinical trial comparing pregabalin with placebo over a 12-week treatment period in patients with spinal cord injury who had central neuropathic pain as defined by the International Association for the Study of Pain classification. The 12-week treatment period was preceded by a 1-week baseline period during which baseline data were collected. Patients were randomised to receive either flexible dose pregabalin (150-600 mg/day) (n=70) or placebo (n=67) taken twice daily. The primary endpoint of the study was mean pain score as measured by patient pain diary assessments which were completed daily. Patients also rated the extent to which pain interfered with sleep in a daily diary. Changes in anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS).


Results from the study showed that:

- Patients receiving pregabalin experienced significant improvements in symptoms as early as the first week of treatment and those improvements were sustained throughout the study

- Patients receiving pregabalin experienced a significant reduction in the average intensity of their pain and significant improvements in pain-related sleep interference (p<0.001) as well as a reduction in anxiety (p<0.05) compared to those taking placebo (p<0.001)

- More than 40 percent of patients had greater than a 30 percent reduction in pain as compared to 16 percent of patients on placebo (p=0.001)

- At the end of the study, three times less patients had severe pain in the pregabalin group compared with the placebo group

- Pregabalin was associated with a rapid and significant reduction in pain-related sleep interference (p<0.001) as well as a reduction in anxiety (p<0.05) compared to those patients taking placebo

- The most common adverse events were somnolence and dizziness, which were typically mild to moderate and transient.


About the Pain Management Research Institute

The Pain Management Research Institute (PMRI) is headed by Professor Michael Cousins and brings together around 40 researchers and 40 clinical staff who are involved in pain research and management (http://www.pmri.med.usyd.edu.au/). The Institute also has a strong focus on education and has a number of staff involved in the delivery of a postgraduate degree program in Pain Management through the University of Sydney. This course is delivered on-line and accessible to students internationally. In 2004 the PMRI Educational Program received an international award as an "Exemplary Educational Program". Since 2005, the education program has been available to European and North American students through collaborations with the University of Edinburgh and the University of California, San Francisco.

The pain research program of the PMRI has a broad scope and has a number of teams investigating various aspects of pain epidemiology, neurobiology, psychology and treatment and has gained international recognition for its work in several areas including pain following spinal cord injury. In 1998, the Centre gained one of only eight National Health & Medical Research Council (NHMRC) of Australia awards as a "Centre of Clinical Excellence in Hospital Based Research". In 2005, the PMRI, in collaboration with the University of Queensland (Australia), University College London (UK) and Nagasaki University (Japan) was a recipient of an NHMRC Program Grant (2005-2009). Also in 2005 PMRI was the top level funded institution for a Program Grant from the NSW Health to investigate "Mechanisms and Treatment of Pain Associated with Spinal Cord Injury" (2005 - 2008)

The Pain Management & Research Centre (PMRC) is the clinical arm of the PMRI and conducts clinical treatment programs in acute pain, cancer pain and chronic non cancer pain. PMRC comprises a group of approx 40 multidisciplinary health care practitioners who evaluate all aspects of each patient's pain and recommend treatment options based upon a multidisciplinary approach. PMRC currently provides approx 40,000 episodes of patient care per annum. Each year at least four internationally funded Fellows spend a year of training with PMRC. To date Fellows have been drawn from more than 20 countries.


[1] Bonica JJ. Introduction: Semantic, epidemiologic and educational issues. In: Casey KL, ed. Pain and Central Nervous System Disease. New York: Raven Press, 1991:13-30.

[2] Siddall PJ, Taylor DA, McClelland JM, Rutkowski SB, Cousins MJ. Pain report and the relationship of pain to physician factors in the first 6 months following spinal cord injury. Pain 1999;81(1-2):187-197.

[3] Merskey H, Bogduk N, eds. Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Seattle: IASP Press, 1994:209-212.

[4] Cruz-Almeida Y, Martinez-Arizala A, Widerstrom-Noga EG. Chronicity of pain associated with spinal cord injury: a longitudinal analysis. J Rehabil Res Develop. 2005; 42(5):585-594.

[5] Finnerup N, Johannesen I, Fuglsang-Frederiksen A, Bach FW, Jensen T. Sensory function in spinal cord injury patients with and without pain. Brain. 2003; 126:57-70.

[6] Siddall P, McClelland JM, Rutkowski S, Cousins M. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003; 103:249-257.

[7] Ravensscroft A, Ahmed YS, Burnside IG. Chronic pain after SCI: a patient survey. Spinal Cord. 2000; 38:611-614.

[8] Stensman R. Adjustment to traumatic spinal cord injury: a longitudinal study of self-reported quality of life. Paraplegia. 1994; 32:416-422.


Source: Pain Management Research Institute

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Criminal probe into MS ‘wonder drug’

A DRUG company is under criminal investigation for the way it has marketed an unproven “wonder” treatment for multiple sclerosis to thousands of patients.
The firm, Daval International, chaired by a discharged bankrupt described by a High Court judge in 2002 as a liar, has been promoting its drug as a “major scientific breakthrough”.

It is being distributed across Britain using a licence granted by a government agency last year despite serious concerns from doctors and multiple sclerosis (MS) experts.

A Sunday Times investigation has found claims that the company misrepresented research to present the drug, Aimspro, in a more positive light.

The Department of Trade and Industry has expressed concern that the company is trading “on future hope” — taking money from vulnerable investors in the expectation that it will become a clinically proven drug.

So far the drug, which is based on a serum from goats injected with inactive HIV virus, has never been properly tested in full clinical trials to assess its safety and efficacy.

However, the Medicines and Healthcare Products Regulatory Agency (MHRA) and government ministers have allowed it to be sold under a “specials” licence which is not designed for the marketing of drugs.

The MHRA was the body that authorised the so-called “elephant man” drugs trial at Northwick Park hospital, which left six healthy young men critically ill.

A key figure lobbying for the drug has been Lord Elder, a friend of Gordon Brown since their schooldays and former adviser to Tony Blair. The peer, who has £300,000 worth of shares in the company and acts as its paid adviser, attended meetings between Daval executives, Brown and other ministers.

This weekend, following The Sunday Times inquiries, the MHRA disclosed that it had been investigating the drug for some time. It is now understood to be looking into the way Aimspro has been sold and marketed to patients in possible breach of the Medicines Act.

The statement said: “The MHRA is conducting a criminal investigation into an unlicensed medicinal product known as Aimspro which is promoted by Daval International Limited.”

Daval has built significant demand for Aimspro among Britain’s 85,000 MS sufferers. Last month, a petition with more than 20,000 signatures was presented to Downing Street calling for NHS backing for the drug.

Daval and its supporters claim that Aimspro “dramatically” alleviates the symptoms of MS, a chronic disease that attacks the central nervous system. Over the past two years a number of stories have appeared in the media claiming patients have regained eyesight and thrown away their walking sticks after taking the drug. During this time, Daval has raised almost £4m from investors on the promise that Aimspro will one day become a clinically proven drug.

David Shotton, Daval’s chairman and main shareholder, was discharged from bankruptcy shortly before he set up the company. The company’s finance director, Graham Ralph, is also a discharged bankrupt.

Shotton, 65, has twice been castigated by High Court judges. In a 1995 case over a disputed bank loan the judge said he was a “wholly unreliable witness” who had a “willingness to advance claims he knew were unjustified”.

Seven years later another judge found that he had lied to attract funding for business schemes. The judge described Shotton as a “most unsatisfactory and untruthful witness . . . well practised in the use of lies and half truths”.
Asked to comment on his suitability as chairman of a drugs company, Mr Shotton said last week he had been truthful and “it was unfortunate that the judges preferred the evidence of others”.

In six years the company has commissioned only two proper clinical trials of Aimspro. The first, at St George’s hospital, south London, was aborted half way through after a dispute between the hospital and Daval. The other, at the Radcliffe hospital, Oxford, was too small to establish the drug’s safety.

At the time, Daval was claiming that even severe damage to the optic nerve could be repaired by treatment with Aimspro. But the Oxford trial found no evidence to substantiate this.

Nonetheless, a year later Daval wrote to the government claiming that “clinical, scientific and empirical evidence clearly establishes our clients have a product which will bring substantial relief to thousands of sufferers”. It emphasised that the Oxford trial had been “significant” and “successful”.

A key researcher from the Oxford study said last week the results had been “wholly misrepresented” by Daval. Dr Nikos Evangelou, a consultant neurologist at Queen’s medical centre, Nottingham, is also critical of the lack of research: “It’s inappropriate to promote miraculous patient stories without trial results.” Daval said last week it had never claimed that Aimspro could restore damaged eyesight.

The product has been made available to hundreds of patients through GPs who have been prescribing it on an “informed consent” basis. Daval claims that none of these patients has ever reported an adverse reaction.

But The Sunday Times has spoken to the husband of an MS sufferer in Lincolnshire who sent a 30,000-word complaint to the MHRA about the drug. The husband, who does not wish to be named, claims Daval offered his wife free treatment with Aimspro after he agreed to buy £5,000 worth of its shares.

He claims his wife’s condition deteriorated rapidly after she had been given the drug by Dr Ian Brooman, a GP who was also a director of the company. “Within hours there was a reaction and she started going downhill,” he recalls. “It was as if she had been poisoned.”

His wife’s sight grew worse, she had spasms on her left side and suffered severe pain, according to his statement. But Daval refused to believe that the drug was responsible. Later Dr Brooman returned to take a blood test and retrieved the couple’s supplies of Aimspro.

The husband has passed his documents and tapes to the MHRA. However, last week Dr Brooman, who still administers Aimspro and has shares in Daval, said he was “not aware” of any “reported adverse reaction” from his patients.

The complaint was made in late 2004 and the MHRA is still investigating. Last week Daval said: “Clinicians are currently treating over 200 patients with Aimspro and there have been no reports of adverse reactions.”

The drug has been the subject of an extensive lobbying campaign. In March 2003, Lord Elder attended a meeting at the Treasury in which Shotton and his team met the chancellor for talks. In the meetings, Daval directors described the product and its “remarkable performance”. The purpose of the talks was to obtain government funding for further research and to “fast-track” the drug to approval by the regulator.

Discussions were arranged in 2004 with Lord Warner, the health minister who was then responsible for the MHRA, and Liam Donaldson, the government’s chief medical adviser.

Last November Daval had a breakthrough when the firm it uses to manufacture the drug was given a “specials” licence by the MHRA. “Specials” are intended to certify that a manufacturer can safely make a drug on the request of a doctor as a one-off for a specific patient.

Documents seen by The Sunday Times indicate that Daval was encouraged by health ministers and the MHRA to go down this route. The “specials” licence is now being used by Daval to make widespread sales of the drug, by-passing the higher regulatory standards of a full marketing licence. It promotes the product on its website at £3,000 for a two-month course.
A source at the MHRA last week described this as “licensing through the back door”. This raises questions about why the company was apparently encouraged to use the “specials” system.

The decision is all the more remarkable as the DTI’s companies investigation branch has been looking into Daval and its chairman for over two years.

The Sunday Times has seen a letter sent to Daval by a Treasury solicitor on behalf of the department in March 2005 which expresses concern about Daval’s relations with investors suffering from MS who, it says, “may be led to understand that making an investment in Daval shares would give them accelerated and/or privileged access to (Aimspro)”. Daval claims this allegation was unfounded.

Daval, which holds its AGM on Tuesday, said last week it had no knowledge of the MHRA investigation. It added: “Over the last 18 months work has gone into improving Aimspro and ensuring it complies with good manufacturing process. Full clinical trials are imminent.”

Yesterday the MS Society came out publicly against the drug: “We advise people against seeking the treatment until (clinical trial) evidence is published and have become increasingly concerned that the drug continues to be promoted and used without it.”

Professor Gavin Giovannoni, an MS specialist at Barts and the London hospitals, said: “This is a very vulnerable group of desperate patients who have a chronic illness. They’re prepared to try anything, and that’s the tragedy of the situation.”


Insight: Michael Gillard, Jonathan Calvert and Gareth Walsh

Physical therapy arrives

Popularity surges for varied reasons
By Judy Foreman | November 27, 2006

So there I was, the quintessential battered athlete, standing in a silly little "johnnie" so physical therapist Susan Lattanzi could put me through my paces.

I had arrived on her doorstep at Mount Auburn Physical Therapy Associates in Watertown because my right shoulder was killing me. I had just joined a swim team and suddenly increased my weekly yardage substantially. By the time I saw Lattanzi, I couldn't swim 15 minutes without my shoulder screeching in protest.

She had me put my arm by my side, thumb facing forward, then lift it overhead alongside my ear. No problem. Then, another arm lift with my palm up and the arm raised to the side to shoulder level. Ouch!

My rotator cuff was damaged, but it felt better within weeks, after physical therapy with ultrasound to improve blood flow, deep friction massage to break up microscopic scarring, and home strengthening exercises. No surgery! Back to swimming!

No one keeps good track of visits to physical therapists, but there is so much demand that there are now more than 200 training programs in the United States, up from 140 just 10 years ago. Physical therapists are also better trained than ever before, with the number getting doctorates soaring.

Despite growing demand, in some ways it's easier than ever to see a physical therapist. Most states allow patients "direct access" without a doctor's referral, though in some cases, insurance companies will not pay for physical therapy without a referral.

"Physical therapy is booming. We can't get them out of school fast enough. Hospitals are crying out for physical therapists all over the country," said Dr. Jeffrey B. Palmer , director of physical medicine and rehabilitation at Johns Hopkins Medical Institutions.

Part of the growing demand is because the population is getting older and creakier. But much of it, particularly for problems like back pain, he said, "is the desire for conservative management."

Dr. Lyle Micheli , an orthopedic surgeon and director of sports medicine at Children's Hospital Boston, said he now sends 90 percent of patients "to physical therapy instead of surgery."

At the Spine Center at New England Baptist Hospital, Dr. Geno Martinez, who specializes in rehabilitation medicine, tells many patients that their back pain will improve if they get moving with the help of a physical therapist. Though some physicians still don't believe it, he said, "in reality, back pain, in general, is not a surgical condition."

Further driving the popularity of physical therapy is the fact that therapists can offer one-stop shopping, not just spinal manipulation or massaging muscles to get rid of tension. Physical therapists offer highly individualized programs of specific exercises and therapy to heal injuries, said Diane Maeda , a physical therapist supervisor at the UCLA Medical Center. By contrast, other physical therapists said, personal trainers in health clubs know how to build muscle but often do not have the lengthy medical training that physical therapists do.

There is also growing evidence of the efficacy of physical therapy for specific problems.

In the old days, physical therapists often stuck to a one-size-fits-all approach, using the same techniques -- massage, heat, stretching -- for everybody. Now they have a much better idea of which techniques work for which symptoms, especially with back pain.

Anthony Delitto , chairman of the department of physical therapy at the University of Pittsburgh, is one of the leaders in the emerging field of "evidence-based" physical therapy. Physical therapists, like others in medicine, are increasingly trying to base their treatments on research showing what works and what doesn't.

Delitto, for instance, has developed "prediction rules" for which patients with back pain will respond to which exercises.

But it's not just back pain that sends people to physical therapists. In addition to shoulder problems like mine, people go for help with neurological diseases such as multiple sclerosis, stroke, and even dizziness, among other things.

For those with multiple sclerosis, said Palmer of Hopkins, physical therapy doesn't change the course of the disease, but it can help them move better within their limits.

For stroke patients, there is "very good evidence that movement therapy can produce changes in the brain, or reprogramming," Palmer said. Brain scans show physical therapy can alter the brain so that a function, like moving an arm, that would normally be controlled by the damaged area of the brain can eventually be controlled by another area.

Anne Hartnett , 61, a Watertown health educator and artist, said physical therapy was tremendously helpful for her headaches and balance problems. Almost two years ago, Hartnett had a virus that attacked her inner ear -- which sends signals that help the brain perceive motion and the body's position in space.

She went to see Janet Callahan , a physical therapist at Massachusetts General Hospital, who taught her a series of exercises in which she keeps her eyes steady on a fixed target while moving her head. Over time, Callahan said, this teaches the brain to respond better to motion and orientation signals from what is remaining of Hartnett's inner ear function.

In the early months of therapy, Hartnett still could not stand and carry on a conversation without getting dizzy. She "lurched" around, she said, and felt that she had to explain to strangers that "I am not a drunk."

The physical therapy, Hartnett said, is slowly giving her back her life: "It is a godsend."

Judy Foreman is a freelance columnist who can be contacted at foreman@globe.com.


© Copyright 2006 The New York Times Company

ECTRIMS 2006 - Diagnosis and Monitoring of Multiple Sclerosis: Focus on Cerebrospinal Fluid Analysis and Brain Imaging CME

Barry A. Singer, MD

Introduction

Cerebrospinal fluid analysis and brain imaging were 2 topics discussed during the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 27-30, 2006, in Madrid, Spain. The highlights of new findings are reviewed, and implications for clinical practice are described.

Cerebrospinal Fluid Analysis

Newer techniques of analyzing cerebrospinal fluid may result in improved diagnosis and prognosis of multiple sclerosis (MS). With an alkaline phosphatase technique to study immunoglobulin (Ig)M oligoclonal bands, the sensitivity for diagnosing MS was shown to be as high as 96.2% in a study of 132 MS patients and 385 patients with other inflammatory central nervous system disorders.[1] The specificity of the testing was even higher at 99.5%. The presence of the IgM subtype of oligoclonal bands is prognostic for the conversion of a clinically isolated syndrome to clinically definite MS. In addition, the finding of IgM oligoclonal bands confers a higher risk for secondary progressive disease (P = .0009), a second relapse within a year, and disability progression to expanded disability system scores of greater than 6. The patients with IgM oligoclonal bands directed at myelin lipids appeared to have a particularly aggressive form of disease.

A larger study confirmed the predictive value of the presence of oligoclonal bands in patients with a clinically isolated syndrome.[2] Of 572 patients with a clinically isolated syndrome, 415 had oligoclonal band testing. The presence of oligoclonal bands almost doubled the risk of developing clinically definite MS at 5 years (hazard ratio, 1.7). Of the total cohort, 61% of patients were oligoclonal band-positive. Only 30% of patients had oligoclonal bands in the cerebrospinal fluid in the group with 0 Barkhof MRI criteria. Sixty-nine percent of patients with 1-2 Barkhof MRI criteria and 85% of patients with 3-4 Barkhof MRI criteria had oligoclonal bands (P < .0001).

Brain Imaging Updates

Interferon beta-1a Studies

The MRI T2 burden of interferon beta-1a given 30 micrograms (mcg) intramuscularly weekly vs 44 mcg subcutaneously thrice weekly was studied in a post hoc analysis of the 48-week data from the Evidence for Interferon Dose Response: European-North American Comparative Efficacy (EVIDENCE) study.[3] The median absolute change in burden of disease was -189.5 mm3 for patients who received the 44-mcg dose and -19 mm3 for patients who received the 30-mcg dose. The adjusted mean treatment difference in percentage change of burden of disease from baseline to week 48 was -4.6% in favor of the 44-mcg thrice-weekly dose (P = .002).

Traboulsee and colleagues[4] presented data on the clinical benefits of subcutaneous interferon beta-1a from the Prevention of Relapses and Disability by Interferon-beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) trial long-term follow-up study. Those patients randomized originally to 44 mcg thrice weekly had a 5.0% increase in T2 burden of disease compared with a 24.5% increase in the late treatment group (P = .002). The 22-mcg thrice-weekly group had a more modest 17.4% increase in disease burden, but this increase was not statistically significant compared with the late treatment group (P = .114).

The effect of interferon beta-1a 30 mcg weekly on black hole volume was studied in a post hoc analysis of 160 patients from the Multiple Sclerosis Collaborative Research Group study.[5] In this study, the median increase in T1-hypointense lesion volume over 2 years was 40 mm3 for treated patients and 124 mm3 for placebo patients. This 68% reduction was statistically significant (P = .045) when adjusted for the number of baseline enhancing lesions. Baseline T2 lesion volume and T1-enhancing lesion volume significantly correlated with T1 hypodensity volume evolution.

Prospective Magnetic Resonance Spectroscopy

Khan and colleagues[6] studied prospective magnetic resonance spectroscopy in 18 relapsing-remitting MS patients on glatiramer acetate and 4 untreated patients over 4 years. N-acetylaspartate to creatine ratio determination was performed as a method of assessing axonal injury. The mean ratio for an area centered around the corpus callosum was 1.97 ± 0.24 at baseline for all 18 patients and 2.21 ± 0.16 at 4 years for the 15 patients still on glatiramer acetate. The mean ratio for normal-appearing white matter was 2.075 ± 0.30 at baseline and 2.27 ± 0.2 at 4 years. The mean ratio conversely dropped from baseline in the untreated patients. The rise in the N-acetylaspartate to creatine ratio in patients taking glatiramer acetate might reflect axonal metabolic recovery.

The BECOME Study

The Betaseron vs. Copaxone in MS with triple-dose gadolinium and 3-T MRI Endpoints (BECOME) study prospectively analyzed T1 hypodensity evolution in relapsing MS patients randomized to receive interferon beta-1b or glatiramer acetate treatment.[7] Enhancing lesions were monitored to assess the development of black holes. Lesions were considered to be permanent black holes when the T1 hypodensities persisted for 12 or more months. With interferon beta-1b, 6 of 45 black holes (13.3%) became permanent at 12 months, and at 9 months, 8 of 37 black holes became permanent. With glatiramer acetate, the permanent black holes developed from 7 of 16 T1 hypodensities (43.7%) at 6 months and from 4 of 7 (57.1%) T1 hypodensities at 9 months. Therefore, fewer lesions evolved to permanent black holes with interferon beta-1b than with glatiramer acetate at 6 months (P = .01) and 9 months (P = .05). Over 12 months of treatment, the T1 hypointense volume decreased 354.1 ± 859.7 mm on interferon beta-1b and 320.5 mm ± 935 mm on glatiramer acetate; this difference was not significant (P = .9). The percentage of the original enhancing lesion area that became a permanent black hole area was smaller with interferon beta-1a than glatiramer acetate (P = .01).

Mitoxantrone Study

Mitoxantrone is approved for the treatment of worsening relapsing-remitting and secondary progressive MS. Walczak and colleagues[8] investigated the development and evolution of T1-weighted lesions, proton density (PD)-weighted lesions, and brain atrophy in MS patients treated with mitoxantrone for 18 months. In total, 23 patients treated with a cumulative dose of 120-140 mg of mitoxantrone over 18 months were compared with 15-untreated MS patients. Although the mean number of new T2 lesions was shown to decrease by 85% with mitoxantrone in the Mitoxantrone in Multiple Sclerosis (MIMS) trial,[9]this trial examined T1 changes. The T1-weighted lesion volume increased by 66.6% in the control group and increased by 43.5% in the mitoxantrone-treated group. Brain parenchymal fraction decreased by 0.581% in the control group and by 0.538% in the mitoxantrone-treated group. Therefore, mitoxantrone favorably reduced the rate of new T1-hypodense lesion volume and reduced the rate of brain atrophy compared with control patients who did not receive treatment.

Magnetization Transfer MRI

Agosta and colleagues[10] examined the value of magnetization transfer MRI in predicting the accumulation of disability. Seventy-three patients with relapsing-remitting, secondary progressive, or clinically isolated syndrome demyelinating disease were studied with magnetization transfer at baseline and 12 months later. Forty-four patients (60%) had significant disability worsening. Independent predictors of worsening disability over a median period of 8 years were the baseline gray matter magnetization transfer ratio histogram peak height (P = .029) and the average lesion magnetization transfer ratio percentage change after 12 months (P = .016). Of interest, the gray matter change was a significant predictor in a primarily white matter disease.

Impact of Higher Magnetic Field Strength

Will higher magnetic field strength aid in the diagnosis and monitoring of MS patients? Stosic-Opincal and colleagues[11] estimated the advantage of 3.0-T over 1.0-T field strength MRI systems in the evaluation and follow-up of patients with MS. Twenty-three patients underwent 1.0-T and 3.0-T MRI imaging on the same day. At 1.0 T, 41 gadolinium-enhancing lesions were detected in 10 of 23 patients. With the 3.0-T MRI system, 51 enhancing lesions, representing a 24.4% increase in the number of lesions, were detected in 13 of 23 patients. The number of lesions on fluid-attenuated inversion recovery images also increased by 14.6% with the 3.0-T MRI system. These data indicate that increased sensitivity in lesion detection can be obtained with high magnetic field imaging.

Pathologic tissue blocks can also demonstrate more lesions in a higher magnet. Schmierer and colleagues[12] explored whether a 9.4-T MRI system is more sensitive at assessing MS pathology than a 1.5-T MRI system. One block demonstrated only a single white matter lesion on a 1.5-T MRI system and 5 lesions on a 9.4-T MRI system. The study authors concluded that a 9.4-T MRI system is a powerful tool to detect white matter lesions in pathologic tissue.

Predicting Disability

The ability to predict a patient's degree of disability, 20 years after a clinically isolated syndrome, would be a powerful tool to assist in treatment decision making. Fisniku and colleagues[13] reported on the correlation of baseline MRI activity with disability status 20 years later. Forty-nine of 57 patients (86%) with T2 MRI lesions at baseline went on to develop clinically definite MS after a mean of 19.5 years. In contrast, only 6 of 30 patients (20%) without T2 MRI lesions at baseline developed clinically definite MS. After 20 years of follow-up for 87 patients, 33 had relapsing-remitting disease, including 22 patients with an expanded disability system score of ≤ 3. Twenty-two patients had developed secondary progressive disease with a median expanded disability system score of 7.5, including 3 patients who had died from severe disease. T2 lesion volume moderately correlated with 20-year disability scores (P < .001).

Dirty-appearing White Matter

Dirty-appearing white matter is a description of diffuse areas of slightly increased signal intensity in the white matter on T2 images, which are distinct from the typically focal high-signal-intensity lesions that are usually well demarcated. Miropolsky and colleagues[14] determined the relationship between dirty-appearing white matter and changes in T2 lesion volume and brain volume in a group of MS patients followed for up to 8 years. Of the 348 patients who returned for 8-year follow-up in the PRISMS study, dirty-appearing white matter was seen in 88 (25.3%) at baseline. Only 3 additional patients developed this white matter change at the 8-year follow-up. For patients with dirty-appearing white matter at baseline, the volume increased in 2.2%, decreased in 28.4%, and remained the same in 69.3% of patients. Patients with dirty-appearing white matter at baseline also had lower T2 burden of disease at baseline (P = .0014). The whole-brain ratio was studied as a marker of brain volume. Patients with dirty-appearing white matter had a larger whole-brain ratio at baseline (P < .001) and a greater reduction in the whole-brain ratio at long-term follow-up (P = .038).

COGIMUS Study

The COGIMUS study evaluated cognitive impairment in 430 early relapsing-remitting MS patients with relationship to MRI parameters.[15] One third of patients exhibited impairment on 2 tests or more in Rao's Neuropsychological Screening Battery. Impairment of spatial recall, symbol-digit modalities, and paced auditory 3-second tests were significantly associated with brain MRI T2 and T1 lesion loads. A significant correlation with brain atrophy was seen with symbol-digit modalities and selective reminding-consistent long-term retrieval tests. Multivariate logistic regression showed that age, disease duration, and T2 lesion load were significant predictors of cognitive impairment. The results from this study confirmed that cognitive impairment can occur early in the disease course and is associated with MRI T2 lesion load, T1 lesion load, and brain atrophy.

Conclusion

The finding of oligoclonal bands in the cerebrospinal fluid almost doubles the risk of developing clinically definite MS. Subtyping oligoclonal bands can increase diagnostic sensitivity and specificity as well as help predict disease progression. MRI studies have demonstrated the benefit of interferon and mitoxantrone on the development of T1 hypodensities. Cognitive dysfunction seen early in MS is associated with increased MRI T2 and T1 lesion load as well as brain atrophy. Magnetization transfer ratio, magnetic resonance spectroscopy, and higher field magnets may all improve disease prognosis and the ability to assess therapeutic response.

References

Alvarez-Cermeno JC. Diagnostic utility of CSF testing and beyond. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Abstract 73.
Tintoré M, Pelayo R, Rovira Á, et al. Do oligoclonal bands add information to baseline MRI in first attacks of multiple sclerosis? Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Abstract 74.

Traboulsee A, AL-Sabbagh A, Bennett R, et al; on behalf of the EVIDENCE Study Group and UBC MS/MRI Research Group. Greater reduction of MRI T2 burden of disease with interferon beta-1a 44 mcg administered subcutaneously three times weekly then 30 mcg administered intramuscularly once weekly: analysis of 48-week data from the EVIDENCE study. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 678.

Traboulsee A, Li D, Kappos L; on behalf of the PRISMS LTFU Study Group and the UBC MS/MRI Research Group. Long-term clinical benefits from subcutaneous interferon beta-1a: a phased analysis of the PRISMS long-term follow-up study. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 677.

Radue EW, Saharain M, Pace A, et al. The evaluation of black hole volume evolution as it relates to lesion load, extent of enhancement, and treatment with intramuscular interferon-beta-1a in two relapsing-remitting multiple sclerosis studies. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 608.

Khan O, Shen Y, Mackenzie M, et al. Prospective long-term study of proton brain magnetic resonance spectroscopy in relapsing-remitting multiple sclerosis: effect of glatiramer acetate on axonal injury. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 171.

Cadavid D, Gómez-Choco M, Alemany M, et al. Outcome of T1 hypodensities in patients with early forms of multiple sclerosis randomised to Betaseron or Copaxone and followed prospectively by monthly 3T MRI for up to 2 years: preliminary analysis of the BECOME study. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 365.

Walczak A, Berkowicz T, Wartolowska K, et al. Effect of mitoxantrone therapy on T1 lesion load and atrophy in multiple sclerosis patients. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 609.

Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomized, multicentre trial. Lancet. 2002;360:2018-2025.

Agosta F, Rovaris M, Pagani E, et al. Magnetisation transfer MRI metrics predict the accumulation of disability eight years later in patients with multiple sclerosis. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 198.

Stosic-Opincal T, Gavrilov M, Lavrnic S, et al. Comparison of 1.0T and 3.0T MRI findings in follow-up of patients with multiple sclerosis. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 190.

Schmierer K, Parkes HG, So PW, et al. High field-high yield: detecting multiple sclerosis white matter lesions at 9.4 tesla. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 191.

Fisniku L, Brex P, Altmann DR, et al. Disability status and the relationship between the T2-MRI abnormalities in CIS patients and the long-term outcome in a 20-year follow-up. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Abstract 6.

Miropolsky V, Vertinsky T, Zhao GJ, et al. Dirty-appearing white matter in multiple sclerosis: relationship to T2 disease burden increase and brain volume decrease with 8-year long-term follow-up. Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Poster 621.

Patti F, Amato MP, Tola MR, et al. Cognitive impairment and MRI features in early relapsing-remitting multiple sclerosis patients: results of an Italian multicentre study (COGIMUS). Program and abstracts of the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis; September 27-30, 2006; Madrid, Spain. Abstract 82.