New Formulation of Multiple Sclerosis Treatment Rebif Approved in European Union

New formulation of Rebif® designed to improve injection tolerability

GENEVA, Switzerland, August 30, 2007 – Merck Serono, a division of Merck KGaA, announced today that the European Commission has granted a marketing authorization for a new formulation of Rebif® (interferon beta-1a) for the treatment of relapsing multiple sclerosis (MS). The new formulation of Rebif® has been developed to increase treatment benefit by improving injection tolerability while targeting an improved immunogenicity profile. This new formulation originates from an innovative approach, using state-of-the-art technologies.

“The European approval of the new formulation of Rebif® is an important step in our efforts to continuously provide enhanced therapeutic solutions for patients with MS,” said Roberto Gradnik, Head of Merck Serono’s Operations for Europe. “We are pleased to bring this enhanced treatment option to patients throughout Europe.”

The European Commission decision applies to all 27 countries in the European Union1, as well as Iceland, Liechtenstein and Norway. Launches of the new formulation of Rebif® in the various countries of the European Union will start in September 2007. The new formulation of Rebif® will be available in the same strengths and pharmaceutical forms as currently registered, i.e. 8.8, 22 and 44 mcg, as a solution for injection in pre-filled syringes.

“The European approval of the new formulation of Rebif® is good news for patients with MS,” said Professor Per Soelberg Sørensen, Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital. “This new formulation will represent an improvement in the therapy of MS patients being treated with Rebif®.”

Rebif®, which was originally approved in Europe in 1998, has been proven effective on the following three key measures of treatment effectiveness: MRI lesion area and activity, relapse rates, and disability progression. The safety and efficacy of Rebif® are supported by a robust long-term clinical development program including comparative studies and 13 years of patient experience from around the world.

The new formulation of Rebif® is the latest of many product developments from Merck Serono to continuously enhance the convenience and tolerability of Rebif®. Other enhancements have included the Rebiject II auto-injector to facilitate injections; a 29 gauge-5 bevel needle pre-filled syringe, the thinnest needle in a ready-to-use pre-filled syringe for the treatment of MS; and a titration pack designed to make starting on Rebif® therapy easier and more convenient.

1 Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, The Republic of Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom


About Rebif®

Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS) and is similar to the interferon beta protein produced by the human body. Interferon helps modulate the body’s immune system, fight disease and reduce inflammation.

Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 80 countries worldwide. Rebif® has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area[1]. Rebif® is not approved for treatment of chronic progressive MS. Rebif® is available in a 22 mcg and 44 mcg ready-to-use pre-filled syringe and a titration pack (8.8 mcg).

Most commonly reported side effects are injection site disorders, flu-like symptoms, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors.


About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. In addition to Rebif®, the Company also offers a second therapy within its US portfolio of MS therapies: Novantrone® (mitoxantrone for injection concentrate) for worsening forms of MS. Full prescribing information for these products can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including oral cladribine, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.


About multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory condition of the nervous system and is the most common, non-traumatic, neurological disease in young adults. The World Health Organization estimates that up to 2.5 million people suffer from MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.


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Forward-looking statements
Some of the statements in this press release are forward looking. Such statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of Merck Serono S.A. and affiliates to be materially different from those expected or anticipated in the forward-looking statements. Forward-looking statements are based on Merck Serono’s current expectations and assumptions, which may be affected by a number of factors, including those discussed in this press release and more fully described in Serono’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on February 28, 2006. These factors include any failure or delay in Merck Serono’s ability to develop new products, any failure to receive anticipated regulatory approvals, any problems in commercializing current products as a result of competition or other factors, our ability to obtain reimbursement coverage for our products, the outcome of any government investigations and litigation. Merck Serono is providing this information as of the date of this press release, and has no responsibility to update the forward-looking statements contained in this press release to reflect events or circumstances occurring after the date of this press release.


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About Merck Serono

Merck Serono, the new division for innovative small molecules and biopharmaceuticals of Merck was established following the acquisition of Serono and the integration of its business with the former Merck Ethicals Division. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, produces and commercializes innovative products to help patients with diseases with unmet needs. Our North American business operates in the United States and Canada under EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), metabolic and cardiometabolic disorders (Glucophage®, Concor®, Saizen®, Serostim®), as well as psoriasis (Raptiva®). With an annual R&D investment of EUR 1bn, we are committed to growing our business in specialist-focused therapeutic areas such as Neurology and Oncology, as well as new therapeutic areas potentially arising out of our research and development in autoimmune and inflammatory diseases.


About Merck

Merck is a global pharmaceutical and chemical company with sales of EUR 6.3 billion in 2006, a history that began in 1668, and a future shaped by 35,091 employees in 62 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.


For more information, please visit www.merckserono.net or www.merck.de

Hormone Helps MS Brains

(Ivanhoe Newswire) -- A hormone better known for easing hot flashes in postmenopausal women may also help protect the brains of people with multiple sclerosis (MS).

UCLA researchers found a specific form of estrogen kept the brain from degenerating in mice that were bred to have the animal form of MS. When researchers looked at spinal cord tissue from mice with MS who were treated with estrogen, they found similar numbers of neurons as seen in healthy mice. Mice with MS who did not receive estrogen had significantly fewer neurons.

The finding is important because there are currently no good treatments available to protect the brain from degeneration due to MS. But the researchers are also excited because the benefit came without raising the risk of breast or uterine cancer in the animals. Estrogen has been linked to higher risks of breast cancer in women taking the hormone to treat postmenopausal symptoms.

The investigators hope to see their results lead to a new "designer estrogen" aimed at protecting the brain not only in MS, but in other conditions as well, including Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, and spinal cord injury. They even see potential in warding off the signs and symptoms of normal aging.

This article was reported by Ivanhoe.com, which offers Medical Alerts by e-mail every day of the week. To subscribe, click on: http://www.ivanhoe.com/newsalert/.

SOURCE: Proceedings of the National Academy of Sciences, published online August 27, 2007

NICE Officially Recommends Tysabri for Severe Multiple Sclerosis

The UK’s National Institute for Health and Clinical Excellence (NICE) officially recommended the use of Biogen Idec/Elan’s Tysabri for the treatment of rapidly evolving severe relapsing-remitting multiple sclerosis (RES), NICE said Aug. 22.

The firms originally announced the NICE recommendation in July when they said reimbursement for Tysabri (natalizumab) by the UK’s National Health Service should commence in a few months.

However, the product was not recommended for use in a subgroup of multiple sclerosis patients that have failed to respond to treatment with beta interferons, such as Bayer Healthcare’s Betaseron, Merck KGaA’s Rebif and Biogen’s Avonex.

Although Tysabri has been approved by the European Medicines Agency for the treatment of multiple sclerosis in patients that exhibit high disease activity despite treatment with beta interferon, NICE said the clinical effectiveness of the product has not been fully established to support use of the product in that setting.

No new brain infection cases with MS drug Tysabri

BOSTON, Aug 28 (Reuters) - Biogen Idec Inc. (BIIB.O: Quote, Profile, Research) said on Tuesday that as of mid-July there have been no new reported cases of a potentially deadly brain infection in patients taking its multiple sclerosis drug Tysabri.

The Cambridge, Massachusetts-based biotechnology company made the disclosure as part of a slide presentation for a conference in Belgium.

According to the slide, there have been no new reports of progressive multifocal leukoencephalopathy, or PML, a rare brain disease since mid-July, which means there have been no new reports of the disease since the drug was reintroduced to the market a year ago. Tysabri, developed with Irish drugmaker Elan Corp. (ELN.I: Quote, Profile, Research), was taken off the market in 2005 after being linked with three cases of the infection. The U.S. Food and Drug Administration allowed the drug back last July because it is effective and patients asked for it to be returned.

Through mid-July, 2007, there were about 14,000 patients taking Tysabri worldwide, of which roughly 12,900 were commercial patients and 1,000 clinical trial patients.

Tysabri is available in the United States through a safety-monitoring program known as TOUCH. All prescribers, infusion sites and patients are required to enroll in the program, which is designed to monitor patients for any signs or symptoms of PML.

(Reporting by Toni Clarke)

((Editing by Dave Zimmerman, Reuters Messaging, toni.clarke.reuters.com@reuters.net, 617-367-4165)) Keywords: BIOGEN TYSABRI

(C) Reuters 2007. All rights reserved. Republication or redistribution ofReuters content, including by caching, framing or similar means, is expresslyprohibited without the prior written consent of Reuters. Reuters and the Reuterssphere logo are registered trademarks and trademarks of the Reuters group ofcompanies around the world.nN28232161

Possible New MRI Marker for Multiple Sclerosis Progression

By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.

BOSTON, Aug. 28 -- Bright spots commonly seen on T1 magnetic resonance imaging brain scans of multiple sclerosis patients may help predict risk of disease progression, researchers here said.

The number of these hyperintense lesions was also significantly correlated with physical disability (P=0.04) and brain atrophy (P≤0.001), found Rohit Bakshi, M.D., of Harvard and Brigham and Women's Hospital, and colleagues.

The findings of their retrospective study suggest that these lesions could be a new clinically relevant biomarker for multiple sclerosis, they wrote in the September issue of the journal Radiology.

Hyperintense lesions on T2-weighted MRI have been used for diagnosis and monitoring of multiple sclerosis, but the clinical correlations have seemed weak, they noted.

"Clearly, there is a need for better MRI markers of disease activity and tissue damage," they wrote.

So, the researchers retrospectively reviewed a database of 145 consecutive multiple sclerosis patients referred to a community-based comprehensive MS center from 1995 to 1999.

The majority of patients were women (77%) and had relapsing-remitting multiple sclerosis (63%). The remaining 34% had secondary-progressive disease. Those with primary-progressive disease were excluded. The mean disease duration was 9.6 years.

Two researchers blinded to patients' clinical details reviewed MRIs from each patient and found that 78% had T1 hyperintense lesions with a mean of 2.3 lesions per patient.

The lesions were typically seen in the supratentorial regions of the brain, particularly the superior and inferior frontal lobes and the superior parietal lobe.

More than a third of the lesions showed up with uniform hyperintensity (38%), but the majority showed hyperintensity only around the rim of the lesion (62%). The average diameter was 0.8 cm.

Patients with more advanced clinical disease were significantly more likely to have multiple than single T1 hyperintense lesions (P<0.001). The findings were:

71% of patients with secondary progressive disease had multiple lesions whereas only 8% had single lesions.
46% of patients with relapsing-remitting disease had multiple lesions whereas 30% had single lesions.

Total number of T1 hyperintense lesions was also significantly correlated with more advanced disease (P=0.003), although the number of T2 hyperintense lesions was not (P=0.059).

"Thus, only the T1 hyperintense lesion subtype was associated with advancing clinical disease course," the researchers noted.

The same pattern was seen for physical disability and brain atrophy, in which T1 lesions were weak-to-moderate predictors but significant whereas T2 lesions were not.

The researchers found that the total number of T1 hyperintense lesions was significantly correlated with physical disability score on the Expanded Disability Status Scale (P=0.04), whereas the total number of T2 hyperintense lesions was not (P=0.14).

Total cortical brain atrophy was significantly associated with the total number of T1 hyperintense lesions on univariate analysis (P<0.001) and after adjusting for disease course (P=0.001).

Another measure of brain atrophy, third ventricular width, was also associated with the total number of T1 hyperintense lesions on univariate analysis (P<0.001) and after controlling for disease course (P=0.001).

The researchers noted that the findings were limited by the use of various MRI protocols across the retrospectively examined cohort, including inconsistent use of contrast-material enhanced imaging, the cross-sectional design that did not allow study of the evolution of T1 hyperintense lesions, and the lack of a quantitative analysis of T1 hyperintensity or relaxation time.

Prospective studies are needed to evaluate multiple T1 protocols, "to see whether the effect is technically dependent;" to incorporate newer techniques, such as diffusion-tensor imaging and MR spectroscopy; and to assess prediction of clinical progression, they said.

"On the basis of these limitations, we urge caution that the results and conclusion of this study should be treated as exploratory and require confirmation in a larger prospective study," they wrote.

Meanwhile, they suggested that physicians should look for hyperintense lesions on nonenhanced T1-weighted MR images "as these may provide useful diagnostic information."

"For the proper evaluation of the presence of gadolinium-based contrast agent enhancement on contrast-enhanced images," they added, "nonenhanced images should be examined concurrently to determine whether hyperintensity on contrast-enhanced images is related to enhancement or to intrinsic T1 shortening in lesions."

Dr. Bakshi reported support in part by grants from the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, and the National Science Foundation. The researchers reported no conflicts of interest.
Additional Multiple Sclerosis Coverage

Primary source: Radiology
Source reference:
Janardhan V, et al "Multiple Sclerosis: Hyperintense Lesions in the Brain on Nonenhanced T1-weighted MR Images Evidenced as Areas of T1 Shortening" Radiology 2007;244:823-831.

Researchers find statins slow onset of Alzheimer's

James Randerson Science correspondent
The Guardian

Tuesday August 28 2007

The cholesterol-lowering drugs statins may also slow the onset of Alzheimer's disease, according to US researchers who examined the brains of 110 elderly people after they died. They found the brains of patients who had not taken the drugs were more likely to show signs of the disease.

Previous studies have suggested that statins have a protective effect against the brain-wasting disease, but the science is contradictory. "Our study is the first to compare the brains of people who had received statins with those who had not," said Gail Li at the University of Washington.

Around 500,000 people in the UK have Alzheimer's, with around one in 20 of those aged over 65 affected. The risk increases with age and by 85 nearly half of people have developed the disease. Statins are drugs that are thought to prevent heart attacks and strokes by reducing the level of the "bad" LDL cholesterol in the blood. They have been hailed as "wonder drugs" because they have few side-effects and can be prescribed for long periods. They have even shown promising results against diseases such as rheumatoid arthritis and multiple sclerosis.

Dr Li and her colleagues took advantage of an existing study into the health of older people to investigate whether statins had an effect on Alzheimer's disease progression. More than 2,500 volunteers had originally been recruited with no health problems in 1994.

The team was given access to the brains of 110 patients who had given permission for their organs to be used in research. Of these, 36 had received at least three prescriptions for statins.

The team found after dissecting the brains that these individuals were less likely to have neurofibrillary tangles - markers of Alzheimer's progression.

"To our knowledge, this is the first study demonstrating an association between statin exposure and neuropathologic changes associated with Alzheimer's disease," the team write in the journal Neurology today.

"These results are exciting, novel, and have important implications for prevention strategies," said co-author Eric Larson, the executive director of the Group Health Centre for Health Studies. However, he stressed that the finding would need to be confirmed.

guardian.co.uk/science ...#8805;

Scientist's simple test detects brain ills

By Maura Lerner Minneapolis Star Tribune
Article Last Updated: 08/22/2007 10:31:21 PM MDT

A University of Minnesota scientist says he has discovered a way to detect Alzheimer's disease, schizophrenia and other brain disorders by using a device that tracks magnetic signals in the brain.

Professor Apostolos Georgopoulos calls it an "elegantly simple test" that has been surprisingly accurate so far in assessing nearly 300 patients and healthy volunteers.

Although the research is still in its early stages, it could lead to a relatively quick and painless test for a wide range of conditions that affect the brain, experts say.

Georgopoulos and his research team used a technology known as MEG (magnetoencephalography) at the VA Medical Center in Minneapolis to study people's brains as they stared at a point of light for 45 to 60 seconds.

In a study published online Wednesday by the British Journal of Neural Engineering, they found they were able to identify six types of disorders "with 100 percent accuracy" - Alzheimer's, chronic alcoholism, schizophrenia, multiple sclerosis, Sjogren's syndrome (an autoimmune disease) and facial pain.

What they found, Georgopoulos said, is that each disease affects the brain differently and alters the way brain cells communicate with one another.

There are no such tests for most brain diseases, which can be difficult to diagnose. They're usually identified over time by observing behavior, such as memory loss in Alzheimer's patients, and other external symptoms.

Georgopoulos, who is internationally known for his work on how the brain affects movement, said even he was surprised by the apparent accuracy of the test. But the results have continued to hold up, he said, even after they concluded the initial study, which involved 142 patients.

"We're approaching our 300th subject," he said, "and it looks better and better."

If it pans out, the new test could be used to diagnose brain disorders earlier, monitor their progress and track the effectiveness of new treatments.

TYSABRI® DEMONSTRATES SIGNIFICANT HEALTH-RELATED QUALITY-OF-LIFE IMPROVEMENTS FOR MULTIPLE SCLEROSIS PATIENTS IN STUDY PUBLISHED IN ANNALS OF NEUROLOG

Cambridge, MA and Dublin, Ireland - August 20, 2007 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today the publication of results demonstrating that patients treated with TYSABRI® (natalizumab) showed a significant improvement in health-related quality-of-life (HRQoL) measures when compared to placebo. These results are from the first Phase III multiple sclerosis (MS) studies that have demonstrated improvement on HRQoL measures in patients with relapsing forms of MS. The results have been published in today's issue of Annals of Neurology.

"These data showed that patients treated with TYSABRI were more likely to experience statistically important improvement in the quality-of-life measures used to assess meaningful disease improvement or progression. These findings have not been previously observed in clinical studies involving MS patients," said Richard Rudick, MD, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, the lead investigator of the study.

These two-year, randomized, double-blind, placebo-controlled, multicenter, Phase III clinical trials (AFFIRM and SENTINEL) were conducted in 2,113 patients with relapsing forms of MS. The objective was to assess the relationship between disease activity and HRQoL in relapsing forms of MS, and the impact of TYSABRI on these measures.

In the studies, HRQoL was assessed using two different measures at baseline and weeks 24, 52 and 104:

The Short Form-36 (SF-36), a standardized, well-validated survey that has been used extensively in many disease areas, including MS to review health status. The SF-36 is comprised of 36 questions designed to assess physical (Physical Component Summary or PCS) and mental (Mental Component Summary or MCS) well-being from the perspective of the patient.

The Visual Analogue Scale (VAS), a measure of well-being as assessed by the patient and marked on a scale of 0 to 100, with 0 indicating "poor" and 100 indicating "excellent."

Results from the AFFIRM monotherapy trial include:

A statistically significant improvement in SF-36 PCS beginning at week 24 and all subsequent time points compared with a decline in the placebo-treated group.

A statistically significant improvement in SF-36 MCS at week 104 compared with a decline in the placebo-treated group.

Statistically significant benefits using the VAS when compared with placebo at week 52 and at week 104.

Patients showed sustained improvement from baseline quality-of-life measures, not just a slowing down of quality-of-life deterioration.

HRQoL measures correlated with common measures of MS severity, including EDSS, sustained disability progression, relapse number, MSFC and volume of T2-hyperintense and T1-hypointense lesions.

Improvements on quality-of-life measures were also observed in the SENTINEL study, in which TYSABRI was added to AVONEX® (Interferon beta-1a). This publication is in addition to a presentation of preliminary results from the same study presented at the 2006 American Academy of Neurology Annual Meeting.

About TYSABRI
TYSABRI is a treatment approved for relapsing forms of MS in the United States and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, after two years, TYSABRI treatment led to a 68% relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54% (p<0.001).

TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Other serious adverse events that have occurred in TYSABRI-treated patients included hypersensitivity reactions (e.g., anaphylaxis), infections, depression and gallstones. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of whom were receiving concurrent immunosuppressants. Herpes infections were slightly more common in patients treated with TYSABRI. In MS trials, the incidence and rate of other serious and common adverse events, including the overall incidence and rate of infections, were balanced between treatment groups.

Common adverse events reported in TYSABRI-treated patients include headache, fatigue, infusion reactions, urinary tract infections, joint and limb pain, lower respiratory infections, rash, gastroenteritis, abdominal discomfort, vaginitis, and diarrhea.

In addition to the United States and European Union, TYSABRI is also approved in Switzerland, Canada, Australia and Israel. TYSABRI was discovered by Elan and is co-developed with Biogen Idec.

For more information about TYSABRI please visit www.tysabri.com, www.biogenidec.com or www.elan.com, or call 1-800-456-2255.

About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Elan
Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself to bringing innovations in science to fill significant unmet medical needs that continue to exist around the world. Elan shares trade on the New York, London and Dublin Stock Exchanges. For additional information about the company, please visit www.elan.com.

Safe Harbor/Forward-Looking Statements
This press release contains forward-looking statements regarding TYSABRI. These statements are based on the companies' current beliefs and expectations. The commercial potential of TYSABRI is subject to a number of risks and uncertainties. Factors which could cause actual results to differ materially from the companies' current expectations include the risk that we may be unable to adequately address concerns or questions raised by FDA or other regulatory authorities, that concerns may arise from additional data, that the incidence and/or risk of PML or other opportunistic infections in patients treated with TYSABRI may be higher than observed in clinical trials, or that the companies may encounter other unexpected hurdles. Drug development and commercialization involves a high degree of risk.

For more detailed information on the risks and uncertainties associated with the companies' drug development and other activities, see the periodic and current reports that Biogen Idec and Elan have filed with the Securities and Exchange Commission. The companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.


For more information contact:

Media Contacts:
Biogen Idec

Shannon Altimari
Ph: 617 914 6524

Elan

Jonathan Birt
Ph: 212 850 5664

Elizabeth Headon
Ph: 353 1 498 0300

Investor Contacts:
Biogen Idec

Eric Hoffman
Ph: 617 679 2812

Elan

Chris Burns
Ph: 353 1 709 4444
800 252 3526

Biopartners Submits Its Novel Interferon beta-1a, Biferonex, To The EMEA

BAAR, Switzerland--(BUSINESS WIRE)--Aug 20, 2007 - Biopartners Holdings AG today announced that it has submitted a marketing authorization application for Biferonex(R) (interferon beta-1a) to the EMEA. Biferonex represents a fully innovative, pH neutral and human serum albumin (HSA) free formulation providing an optimized interferon beta treatment solution for patients suffering from relapsing remitting multiple sclerosis (RRMS).

The submission was welcomed by Professor O. R. Hommes, Chairman of the European Charcot Foundation which coordinates MS research in Europe. "Most impressive are the effects of Biferonex in reducing the size and the activity of inflammatory regions in the brain of MS patients as shown by MRI. This may reduce progression of the disease" he stated.


Interferon beta has been extensively studied in multiple sclerosis, exhibiting beneficial effects in both the relapsing-remitting and progressive forms of the disease by inhibiting inflammatory activity and thereby reducing nerve cell damage. It is also thought to inhibit damage to the myelin sheath by both preventing a T cell-mediated auto-immune response to myelin, and reducing the effect of other naturally-occurring compounds that can enhance the auto-immune response.

The Biferonex HSA-free formulation boasts a low incidence of neutralizing antibodies (NABs) therefore optimizing drug treatment effectiveness. Additionally, its neutral pH minimizes the risk of injection site reactions, which should lead to an enhanced tolerability.

About the MS market:

The World Health Organization estimates that multiple sclerosis affects 2.5 million people worldwide and is one of the most common neurological disorders and causes of disability of young adults, especially in Europe and North America.

About Biopartners Holdings AG

Headquartered in Baar, Switzerland, with an affiliate in Germany, Biopartners is a global biopharmaceuticals company and a leader in the emerging field of multi-source biopharmaceuticals. Biopartners' mission is to develop biopharmaceuticals and innovative formulations of "first generation" biopharmaceuticals as well as advanced delivery systems that may improve patient compliance. Biopartners is developing a comprehensive range of biopharmaceutical products that may offer life-saving therapeutic benefits across many therapeutic areas. By now, Biopartners has submitted three dossiers to the EMEA and has a fourth product in phase III on the way. In March 2007, Biopartners was acquired by a Polish biotechnology company, Bioton S.A.

Contact

Biopartners Holdings AG
Marie-Joëlle Gaufrès, +41 (0)41 766 20 80
Head of Commercial Operations
marie-joelle@Biopartners.ch

Chronic stress can cause or exacerbate MS

Stressed mice unable to fight illness: Study

CBC News

It's long been thought that stress is harmful to your health, but a new study finds chronic stress may increase a person's risk of developing or accelerating a neurodegenerative disease like multiple sclerosis.

Researchers have demonstrated for the first time that inflammation brought on by stress leads to the worsening of the mouse equivalent of MS.



In studies, stressed mice produced a cytokine which is released during stress. That cytokine increased the severity of an MS-like illness in the mice.

The findings were presented Friday at the annual convention of the American Psychological Association.

In the study, scientists simulated stressful situations on mice infected with Theiler's murine encephalomyelitis (TMEV), an acute infection of the central nervous system which is followed by a chronic autoimmune disease similar to that seen in humans with MS.

Another group of mice was also infected but not exposed to stress.

Researchers found that the stressed mice produced a cytokine — interleukin-6 (IL-6) — which is released during stress and regulates the part of the immune system that fights infection. IL-6 increases the severity of the MS-like illness.

Stressed mice were unable to clear the virus from their systems and had higher levels of inflammation, while the non-stressed mice had lower levels of the virus in their bloodstreams and less inflammation, researchers found.

They also discovered that injecting an antibody into the brain that neutralizes IL-6 prior to the stressful episode prevented the stress-related worsening of the disease, said the authors.

Blocking IL-6 halts disease

By blocking the elevation of IL-6, the TMEV infection was weakened, which decreased symptoms such as motor impairment, inflammation in the brain and spinal cord and the viral level in the central nervous system, researchers found.

Based on these findings, Mary Meagher, the lead researcher, theorizes that the adverse effects of stress-induced IL-6 on TMEV infection create a pro-inflammatory environment that interrupts a person's immune response to infection.

Scientists believe that the effects of stress on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine.

Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressants, omega-3 fatty acids and relaxation training.

However, researchers say human clinical trials are needed to determine what preventive approaches will work.

Mainers have higher rate of MS than rest of nation

By Nicole Heanssler

BELFAST (Aug 17): Maine has a 70 percent higher rate of multiple sclerosis than the national average. According to Dr. James Stevenson, neurologist at Waldo County General Hospital, one in 400 people in Maine is affected, whereas the national average is one in 1,000.

The National Multiple Sclerosis Society lists this disease as the most frequent cause of nontraumatic neurological disability in early to middle adulthood.

Why is the number so high in Maine? Research has shown there is a link between a person’s geographic location during adolescence and the risk of developing MS, among other factors.

In March, Stevenson joined the active medical staff at Waldo County General Hospital. He treats neurological disorders, including headache disorders, and has a keen interest in treating patients with MS.

He recalled his first experience treating patients with MS. When a partner of his was retiring he took on some of his colleague’s case load, which happened to include a group of MS patients. In the course of treating them, Stevenson found that the challenge and the unknowns of the disease intrigued him.

“In a way, MS chose me and with my scientific background, academic interest and the challenge of treating the disease, I expanded on my opportunity to treat patients with this disease,” he said.

Word of his interest in treating MS quickly traveled through the extensively networked MS community, allowing him to treat patients with many differing symptoms and stages of the disease.

Multiple sclerosis, believed to be an autoimmune disease, is a chronic neurological disease that affects the brain and spinal cord resulting in the loss of muscle control, vision, balance and sensation.

The disease is more common in women, is partly genetic and tends to affect individuals with a Northern European ancestry at a higher rate than those with other ethnic backgrounds. Researchers haven’t found the exact cause but believe genetics, environmental triggers and a person’s geographic location are significant factors that contribute to the disease.

Stevenson suggests that possibly infectious and/or environmental triggers, which comprises two-thirds of the risk, combined with a genetic factor, which is one-third of the risk, may be the underlying cause for an individual developing MS.

Individuals who live in northern latitudes tend to have more of a risk of developing MS than those who live closer to the equator, he said.

Symptoms may present themselves in several ways but most common are muscular and visual symptoms such as muscle weakness, lack of coordination, blurred vision or double vision.

For a more detailed list of symptoms or information, visit the National Multiple Sclerosis Society website — nationalmssociety.org. MS is diagnosed through clinical evaluations assisted by MRI (magnetic resonance imaging) and other testing.

There is no cure for MS. Six medications help reduce the impact of the disease. When diagnosis is confirmed, medication therapy is begun to lessen the symptoms and frequency of attacks that accompany MS. Four of the six medications can be administered at home and the other two, Tysabri and a chemotherapeutic agent, are administered in a clinical setting through intravenous infusions.

Patients of Stevenson who are prescribed the IV therapies, may have their treatment administered locally at the hospital’s Oncology and Infusion Therapy department.

Stevenson also noted that therapy has a high success rate in reducing the frequency of attacks by one-third or two-thirds.

Because of his extensive experience in treating MS, Stevenson is an appointed member of the clinical advisory committee for the Maine chapter of the National Multiple Sclerosis Society and speaker on behalf of the Maine chapter’s self-help groups. He is also a consultant and speaker for patient and physician audiences locally and nationally for the National Multiple Sclerosis Society and for various pharmaceutical firms.

Stevenson’s office, Belfast Neurology Associates, is located in the Cobb Medical Building, Suite 102, 16 Fahey St. For more information, call 930-2695.

Waldo County General Hospital is a not-for-profit community hospital that has been caring for neighbors since 1901.


VillageSoup/Waldo County Citizen Editor Beth Staples can be reached at 207-338-0484 or by e-mail at bstaples@villagesoup.com.

DNA Vaccine Against Multiple Sclerosis Appears Safe, Potentially Beneficial

CHICAGO, IL -- August 13, 2007 -- A newly developed DNA vaccine appears safe and may produce beneficial changes in the brains and immune systems of individuals with multiple sclerosis, according to an article posted online today that will appear in the October 2007 print issue of Archives of Neurology, one of the JAMA/Archives journals.

In patients with multiple sclerosis (MS), the immune system attacks the myelin sheaths that protect nerve cells in the brain and spinal cord, according to background information in the article. The nerve cell's axon, which transmits messages to other neurons, is eventually destroyed.

The cause of MS is unknown, but evidence points to the involvement of immune cells and antibodies that recognize and attack specific substances in the myelin, such as myelin basic protein. Certain cytokines, small proteins produced by cells that trigger inflammation, also may play a role.

Amit Bar-Or, MD, of the Montreal Neurological Institute and colleagues tested a DNA vaccine, BHT-3009, that encodes a full-length human myelin basic protein. Between 2004 and 2006, the researchers administered the vaccine to 30 patients with relapsing-remitting MS [characterized by symptomatic periods and periods of remission] or secondary progressive MS [when symptoms progressively worsen, but there still may be periods of remission].

After 1, 3, 5 and 9 weeks, participants received intramuscular injections of placebo or BHT-3009 (in doses of.5 mg, 1.5 mg or 3 mg), with or without 80-mg pills of atorvastatin calcium, a lipid-lowering drug previously shown to be effective in autoimmune conditions. After 13 weeks, participants who initially received placebo received four injections of BHT-3009.

Magnetic resonance imaging (MRI) and other safety evaluations were performed at the beginning of the study, and again after 5, 9, 13, 26, 38 and 50 weeks.

"BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI and produced beneficial antigen-specific immune changes," the authors write. These changes included a reduction in the number of cytokine-producing CD4+ T cells (a type of white blood cell) specifically targeting myelin proteins. This reduction was found in the blood as well as in the cerebrospinal fluid of three patients who voluntarily underwent lumbar puncture after completing the course of BHT-3009. Atorvastatin did not appear to provide additional benefit.

"There were no increases in clinical relapses, disability, drug-associated laboratory abnormalities, adverse events or the number and volume of contrast-enhancing [visible on MRI] lesions on brain MRI with BHT-3009 treatment compared with placebo," the authors write. "In fact, there was a trend toward a decrease in the number and volume of contrast-enhancing lesions in the brain in patients treated with BHT-3009 compared with placebo."

Based on these results, a phase 2b trial -- a randomized clinical trial in approximately 290 patients -- of BHT-3009 is already under way. "If successful in MS, antigen-specific DNA vaccines can be developed for prevention or treatment of related diseases, such as type 1 diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis," the authors conclude.

The work described in this article was funded by Bayhill Therapeutics, Inc.


ArchNeurol. 2007;64(10):(doi:10.1001/archneur.64.10.nct70002).


SOURCE: American Medical Association

Functioning Neurons From Human Embryonic Stem Cells Produced

10 August 2007

Scientists with the Institute of Stem Cell Biology and Medicine at UCLA were able to produce from human embryonic stem cells a highly pure, large quantity of functioning neurons that will allow them to create models of and study diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, prefrontal dementia and schizophrenia, etc.

Researchers previously had been able to produce neurons - the impulse-conducting cells in the brain and spinal cord - from human embryonic stem cells. However, the percentage of neurons in the cell culture was not high and the neurons were difficult to isolate from the other cells.

UCLA's Yi Sun, an associate professor of psychiatry and biobehavioral sciences, and Howard Hughes Medical Institute investigator Thomas Südhof at the University of Texas Southwestern Medical Center were able to produce 70 to 80 percent of neurons in cell culture. Sun and Südhof also were able to isolate the neurons and determine that they had a functional synaptic network, which the neurons use to communicate. Because they were functional, the neurons can be used to create a variety of human neurological disease models.

"Previously, the system to grow and isolate neurons was very messy and it was unknown whether those neurons were functioning," Sun said. "We're excited because we have been able to purify so many more neurons out of the cell culture and they were, surprisingly, healthy enough to form synapses. These cells will be excellent for doing gene expression studies and biochemical and protein analyses."

Sun's method prodded human embryonic stem cells to differentiate into neural stem cells, the cells that give rise to neurons. When the time was right, Sun's team added protein growth factors into the cell culture that stopped the neural stem cells from self-renewing and prodded them into differentiating into neurons.

To isolate the cells, Sun and her team added an enzyme that digests a sort of protein matrix that holds cells in culture together. The neurons could then be separated from the neural stem cells that had not yet differentiated, a sort of chemical round-up that isolated the neurons. The cells were then put into a cell strainer that allowed passage through of the isolated neurons.

The large number of pure neurons produced will allow Sun and her team to study their biological form and structure, the genes they express, the development of synapses and the electric and chemical communication activities within the synapse network.

"We will be able to study the cellular properties of neurons in a very defined way that will maybe tell us what goes wrong in diseases such as Alzheimer's and Parkinson's," Sun said. "We're currently creating many models of human neurological diseases that may provide the answers we're looking for. We don't know what causes prefrontal dementia, Huntington's disease or schizophrenia. The key is likely in the quality of neuronal communications. By studying the chemical and electrical transmissions, we may be able to determine what goes wrong that leads to these debilitating diseases and find a way to stop or treat it."

Sun will be among the first researchers to be able to study true neuron function.

A second important discovery in Sun's study showed that two embryonic stem cells lines derived in similar manners, and therefore expected to behave similarly when differentiating, did not. Using the same techniques to prod the two embryonic stem cells lines to differentiate, Sun found that one line had a bias to become neurons that are found in the forebrain. The other line differentiated into neurons found in rear portions of the brain and spinal cord. The finding was surprising, and significant, Sun said.

"The realization that not all human embryonic stem cell lines are born equal is critical," Sun said. "If you're studying a disease found in a certain part of the brain, you should use a human embryonic stem cell line that produces the neurons from that region of the brain to get the most accurate results from your study. Huntington's disease, for example, is a forebrain disease, so the neurons should be differentiated from a cell line that is biased to produce neurons from the forebrain."Sun said there are ways to prod an embryonic stem cell line biased to become neurons found in the rear brain to become neurons found in the forebrain. However, there are limits to how much prodding can be done.

Sun and her team confirmed that the two embryonic stem cell lines were different through gene expression analysis -- neurons that perform different functions in different parts of the brain express different genes. The cell line prone to becoming neurons found in the forebrain expressed genes typically found those neurons, while the other line expressed genes found in the rear brain and spinal cord.

Sun and her team now are studying why the two human embryonic stem cell lines have biases to become different types of neurons.

"If we knew that, we might be able to tweak or alter whatever is driving the bias so that limitation in the stem cell line could be bypassed," Sun said.

Study results were recently published in an early online edition of the journal Proceedings of the National Academy of Sciences.

Source: University of California - Los Angeles (10/08/07)

Nutra Pharma Announces Positive Results of ReceptoPharm Pain Study

Nutra Pharma Corp. (OTCBB: NPHC), a biotechnology company that is developing drugs for HIV and Multiple Sclerosis (MS) has today announced that its drug development holding, ReceptoPharm, has successfully completed a study of RPI-78. RPI-78 is ReceptoPharm’s lead drug candidate being studied for the treatment of pain.

The continuing pain studies, being conducted in collaboration with Soochow University, recently found that RPI-78 was successful in controlling pain with a long duration of effect. A previous study, entitled, “A long-form alpha-neurotoxin from cobra venom produces potent opioid-independent analgesia” was published in the April 2006 issue of Acta Pharmacologica Sinica and explored the pain relieving effects of cobratoxin on laboratory mice. The latest data demonstrated that RPI-78 was as effective as morphine at blocking pain signals in that part of the brain that signals the presence of pain. It was also confirmed that the drug did not use an opioid mechanism. Moreover, the duration of RPI-78’s effect was superior to morphine’s.

“Given the positive results of our study, we plan to continue our efforts to develop RPI-78 as an analgesic,” explained Dr. Paul Reid, CEO of ReceptoPharm, Inc. “We believe that the data from this study and from previous studies may be sufficient to commence a Phase I clinical study in subjects with severe pain,” he added.

Clinical studies with early formulations of RPI-78 revealed that the drug was effective in subjects with pain from terminal cancer, arthritis, headaches and amputations, even where morphine was ineffective. Additionally, the treatment revealed no toxicity and subjects reported no side effects. Low-dose, bi-weekly injections were found to control pain in many subjects for periods reaching 4 years.

“We are very pleased with the positive results of this study as well as results from previous RPI-78 pain studies,” commented Rik J Deitsch, Chairman and CEO of Nutra Pharma Corp. “We believe that these results help us understand more about the use of cobratoxin for treating pain and how it could one day be used as an alternative to Morphine,” he concluded.

About Nutra Pharma Corp.
Nutra Pharma Corp. is a biopharmaceutical company specializing in the acquisition, licensing and commercialization of pharmaceutical products and technologies for the management of neurological disorders, cancer, autoimmune and infectious diseases. Nutra Pharma Corp. through its subsidiaries carries out basic drug discovery research and clinical development and also seeks strategic licensing partnerships to reduce the risks associated with the drug development process. The Company's holding, ReceptoPharm, Inc, is developing these technologies for the production of drugs for HIV and Multiple Sclerosis ("MS"). The Company's subsidiary, Designer Diagnostics is engaged in the research and development of diagnostic test kits designed to be used for the rapid identification of infectious diseases such as Tuberculosis (TB) and Mycobacterium avium-intracellulare (MAI). Nutra Pharma continues to identify and acquire intellectual property and companies in the biotechnology arena.

http://www.NutraPharma.com
http://www.ReceptoPharm.com

This press release contains forward-looking statements. The words or phrases "would be," "will allow," "intends to," "will likely result," "are expected to," "will continue," "is anticipated," "estimate," "project," or similar expressions are intended to identify "forward-looking statements." Actual results could differ materially from those projected in Nutra Pharma's ("the Company") business plan. The Company's business is subject to various risks, which are discussed in the Company's filings with the Securities and Exchange Commission ("SEC"). The positive results of the ReceptoPharm pain study should not be construed as an indication in any way whatsoever of the value of the Company or its common stock. The Company's filings may be accessed at the SEC's Edgar system at www.sec.gov. Statements made herein are as of the date of this press release and should not be relied upon as of any subsequent date. The Company cautions readers not to place reliance on such statements. Unless otherwise required by applicable law, we do not undertake, and we specifically disclaim any obligation, to update any forward-looking statements to reflect occurrences, developments, unanticipated events or circumstances after the date of such statement.

Opexa Therapeutics Receives European Patent Notification for T-Cell Vaccine

THE WOODLANDS, Texas--(BUSINESS WIRE)--Opexa Therapeutics, Inc. (NASDAQ:OPXA), a company involved in the development and commercialization of cell therapies, today announced that it has received notification under Rule 51(4) from the Examining Division of the European Patent Office (EPO) that the EPO intends to issue a patent for “Autologous T Cell Vaccine Materials and Method.” The European patent application is related to a unique method-specific approach for generating a T-cell vaccine that attacks what is believed to be the underlying cause of multiple sclerosis (MS). Rule 51(4) EPC notification is equivalent to a “Notice of Allowance” by the United States Patent and Trademark Office. It is expected that the patent will be granted within the next six months.

David McWilliams, president and chief executive officer of Opexa Therapeutics, commented, “This is an important step in advancing our intellectual property strategy for Tovaxin®, T-cell vaccine for the treatment of MS. Europe represents a significant market as we move forward with our clinical development of Tovaxin and we are pleased that our method has been recognized as being unique.”

About T-cell Vaccination

For a T-cell vaccine to be effective, it should be able to induce T-cell cytotoxic and/or regulatory immune responses against the pathogenic T-cells. Studies of T-cell vaccine have indicated that T-cell vaccination with peripheral blood-derived autologous myelin-peptide selected T-cells in multiple sclerosis patients resulted in the in vivo induction of CD8+ cytotoxic T-cells and CD4+CD25+FoxP3 Tregs specific for T-cell vaccine. The induction of anti-idiotypic cytotoxic CD8+ effector T-cells and anti-ergotypic CD4+CD25+FoxP3 positive Tregs is believed to provide a therapeutically effective dual mechanism of protection to patients treated with Tovaxin. The observed regulatory immune responses have been shown to collectively correlate with clinical improvement in treated patients. Tovaxin is currently in a Phase IIb clinical trial. Patients treated in Opexa’s Phase I/II open-label studies have experienced an approximately 90% average reduction in annualized relapse rate, minimal side effects and observed improvement in average disability (EDSS) scores.

About Opexa Therapeutics

Opexa Therapeutics develops and commercializes cell therapies to treat autoimmune diseases such as MS, rheumatoid arthritis, and diabetes. The Company is focused on autologous cellular therapy applications of its proprietary T-cell and stem cell therapies. The Company’s lead product, Tovaxin®, a T-cell therapy for multiple sclerosis, is in Phase IIb trials. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood. The technology allows large quantities of monocyte derived stem cells to be produced efficiently for use in autologous therapy, thus circumventing the threat of rejection. The Company is in preclinical development for diabetes mellitus. For more information, visit the Opexa Therapeutics website at www.opexatherapeutics.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements about Opexa Therapeutics' growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. These forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Opexa Therapeutics' ability to obtain additional funding, develop its stem cell technologies, achieve its operational objectives, and obtain patent protection for its discoveries, that may cause Opexa Therapeutics' actual results to be materially different from any future results expressed or implied by such forward-looking statements. Opexa Therapeutics undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

Caution Urged in Early MS Treatment

Too Soon for 'Treat-All' Approach to Multiple Sclerosis?

By Daniel J. DeNoon
WebMD Medical News
Reviewed by Louise Chang, MD

Aug. 2, 2007 -- A new study shows that early treatment for multiple sclerosis cuts the risk of disability. But some experts say it's too soon to take a "treat-all approach" to MS.

The international BENEFIT study tested a current trend -- giving MS treatments to patients at the first sign of what might be MS. The study showed that early treatment with Betaseron, one of three forms of beta-interferon approved for MS, cut the three-year risk of disability by 41% compared with delayed treatment.

However, patients who got early treatment only reduced their overall three-year risk of disability by 14%. The final report on the study appears in the Aug. 4 issue of The Lancet. Accompanying the study is an editorial by Mayo Clinic MS expert Sean J. Pittock, MD.

The benefits seen in the BENEFIT study were "modest," Pittock writes. He notes that 12 patients would have to be treated with Betaseron -- beginning at the first sign of MS -- to protect one patient from worsening disability.

Pittock notes that the BENEFIT trial does show, for the first time, that early beta-interferon treatment has a "beneficial effect on accumulation of confirmed disability in patients with a first event suggestive of multiple sclerosis."

But he warns against over-optimistic interpretation of the findings.

"The results should be interpreted with care because the magnitude of benefit, although statistically significant, is clinically small," Pittock writes. The study findings "should not be misconstrued as evidence for a treat-all approach."

In a 2004 study, Pittock and colleagues found that some patients have "benign MS" that does not progress to ever greater levels of disability. Pittock and colleagues suggested that this argues against aggressive, early treatment for all MS patients.

Pittock and colleagues, however, may be bucking a trend. The new findings mean it's time to start treatment when you've had a single MS-like event, says BENEFIT researcher Mark S. Freedman, MD, FRCPC, director of the MS research center at the University of Ottawa, Ontario, Canada.

"The first paradigm shift came at the end of the '90s, when we learned that waiting for an MS relapse is too late and we started treating MS at the time of diagnosis," Freedman told WebMD in May. "Now we see you have to start when you think you have MS. This is the new paradigm shift in MS treatment."

Robert Fox, MD, medical director of Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research, agrees with Freedman.

"We have finally shown that treating MS super early can have a significant impact on the development of disability, which is what patients are most worried about," Fox told WebMD in May.



Discuss this and other MS topics with others on WebMD's Multiple Sclerosis Support Group message board.
SOURCES: Kappos, L. The Lancet, Aug. 4, 2007; vol 370: pp 389-397. Pittock, S.J. The Lancet, Aug. 4, 2007; vol 370: pp 363-364. Pittock, S.J. Annals of Neurology, August 2004; vol 56: pp 303-306. News release, Mayo Clinic, Rochester. Mark S. Freedman, MD, FRCPC, director, MS research center, and professor of neurology, University of Ottawa, Ontario, Canada. Robert Fox, MD, medical director, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic.

© 2007 WebMD, Inc. All rights reserved.

Cytokine Demonstrates Oral Efficacy of Small-Molecule MIF Inhibitors

KING OF PRUSSIA, Pa., Aug. 2 /PRNewswire/ -- Cytokine PharmaSciences, Inc. (CPSI) today revealed that recent experiments with its small-molecule MIF inhibitors showed oral efficacy in animal models. Based on these results, the Company announced that it is advancing one of these compounds into preclinical development.

Macrophage Migration Inhibitory Factor, or MIF, is linked to many conditions, including arthritis, asthma, cancer, sepsis, inflammatory bowel disease and various infections and autoimmune disorders. Neutralization of MIF biological activity has been shown to have a protective effect against these diseases. CPSI has an extensive patent portfolio focused on MIF, covering various methods for neutralization, including small molecules. These compounds were recently shown to be effective in animal models of multiple sclerosis (MS) and arthritis when administered orally.

The MS animal experiments were conducted in the laboratories of Dr. Abhay Satoskar and Dr. Caroline C. Whitacre, both of Ohio State University in Columbus, OH. Dr. Satoskar stated: "The therapeutic efficacy of these compounds was impressive with no outward signs of toxicity. These findings indicate that small-molecule MIF inhibitors are viable drug candidates for treating other autoimmune and inflammatory diseases in which MIF has been identified as a pathogenic factor." Dr. Whitacre adds: "The inhibitors were especially effective in treating disease that had already started, which is traditionally the most difficult hurdle for a new therapy. We are very encouraged by these results."

The arthritis experiments were conducted under the guidance of Drs. Thais M. Sielecki and Vidal F. de la Cruz of Cytokine PharmaSciences, Inc. Dr. Sielecki observed: "We are encouraged to have a small molecule MIF inhibitor that is orally active. MIF is an important target in many diseases and an oral treatment is a definite advantage." Dr. Sielecki will present the MS and arthritis results at the annual American Chemical Society conference on August 22, 2007, in Boston, MA.

Cytokine PharmaSciences is a biopharmaceutical company located in King of Prussia (near Philadelphia), Pennsylvania. The company licenses technologies from academia and other sources, develops products from those technologies and outlicenses the products to third parties for marketing. For more information, visit to http://www.cytokinepharmasciences.com/ .

Website: http://www.cytokinepharmasciences.com/

Landmark Study in The Lancet: Patients Treated With Betaseron(R) After First MS Attack Experienced Significant Delay in MS Progression

WAYNE, N.J., Aug. 2 /PRNewswire/ -- Patients treated with Betaseron(R) (interferon beta-1b) shortly after their first clinical MS event or "attack" showed a 40 percent lower risk of developing confirmed disability progression compared to patients in whom treatment was delayed. The results-which were fast-tracked and published in The Lancet this week-provide the first controlled evidence that delaying Betaseron treatment has an effect on later accumulation of disability, as observed over the three-year study period. No other MS therapy has demonstrated this effect in this early patient population.

The BENEFIT study (BEtaseron in Newly Emerging multiple sclerosis For Initial Treatment), sponsored by Bayer HealthCare, compared Betaseron treatment initiated after a first clinical event with delayed treatment. The study was conducted at 98 sites in 20 countries and included a total of 468 patients.

In the study, investigators measured progression of patient disability using a validated scale called EDSS (Expanded Disability Status Scale)(1) Disability progression was defined as an increase in a patient's EDSS score by at least one point that was confirmed after six months. A confirmed increase by one point in the EDSS scale can be an important and robust predictor of permanent and severe disability later in the disease.(2)

"This research has important implications for the way we treat MS because, for the first time, we have controlled data that irrefutably demonstrates the value of early intervention with effective treatment for patients," said Dr. Ludwig Kappos, Professor of Neurology and Clinical Neuroimmunology at the University of Basel, Switzerland and lead investigator of the BENEFIT study. "These findings support the decision to actively treat patients at the first clinical sign of MS to delay the accumulation of disability."

"We now see real hope for changing the course of disease progression for relapsing MS if people with the disease start an effective treatment like Betaseron right away, rather than wait for further clinical signs of MS to occur," said James Simsarian, M.D., Past President of the Consortium of Multiple Sclerosis Centers (CMSC) and Director of the MS Program at the Neurology Center of Fairfax in Fairfax, Virginia.

Other key findings of the BENEFIT follow-up study include:

-- Sensitivity analyses confirmed the robustness of the main findings.

-- Development of neutralizing antibodies did not have an impact on
disability-related or relapse-related outcomes in the trial.

-- Betaseron was safe and well-tolerated, with the reporting of adverse
events (AEs) similar to those previously reported for the drug.(3)

-- 90 percent of the patients who entered the follow-up study elected to
receive Betaseron treatment, indicating high patient acceptance of
treatment. In the study, methods that may have helped patients stay on
therapy included: the implementation of dose titration at the start of
treatment, the use of an auto-injector to give the injections and co-
medication with an analgesic in the first weeks of treatment.

"Bayer HealthCare revolutionized the treatment of MS when we introduced Betaseron as the first disease-modifying treatment," said Darlene Jody, M.D., Senior Vice President and President of Bayer HealthCare's Specialized Therapeutics Global Business Unit. "The BENEFIT results have the potential to again transform the MS treatment paradigm as they provide convincing evidence that treating patients with Betaseron shortly after the first clinical event suggestive of MS can delay disability progression."

About BENEFIT

BENEFIT is a multi-center trial conducted at 98 sites in 20 countries and included patients presenting with a first clinical episode suggestive of MS and typical MRI findings. The primary outcome measures were time to diagnosis of CDMS, time to confirmed EDSS progression and patient reported Quality of Life outcomes (FAMS-TOI). A total of 468 patients were randomized to receive either 250 micrograms of Betaseron every other day or placebo as a subcutaneous injection in a double-blind fashion. The placebo-controlled treatment period lasted up to 24 months or up to the time when patients experienced a second attack and were diagnosed with clinically definite MS. All study participants were then invited to participate in a follow-up study with Betaseron to prospectively assess the impact of such early versus delayed treatment with Betaseron on the long-term course of the disease for a total observation time of five years. The results reported in The Lancet are from a pre-planned analysis at three years.

About MS

MS is a chronic, progressive disease of the central nervous system and the likelihood of disability increases the longer someone has MS. Symptoms of MS vary from person to person and can be unpredictable. They may include: fatigue or tiredness, dimness of vision in one or both eyes, weakness of one or both legs, numbness and tingling in the face, arms, legs and trunk of the body, spasticity (muscle stiffness), dizziness, double vision, slurred speech and loss of bladder control.

About Betaseron

Betaseron (Interferon beta-1b) is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

Betaseron is the only high-dose, high-frequency interferon beta FDA approved for use in patients after the first attack suggestive MS.

The most commonly reported adverse reactions are lymphopenia, injection- site reaction, asthenia, flu-like symptom complex, headache and pain. Gradual dose titration and use of analgesics during treatment initiation may help reduce flu-like symptoms. Betaseron should be used with caution in patients with depression. Injection-site necrosis has been reported in four percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. See "Warnings," "Precautions," and "Adverse Reactions" sections of full Prescribing Information.

About Bayer HealthCare Pharmaceuticals

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the U.S., Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

1 Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an
expanded disability status scale (EDSS). Neurology 1983; 33: 1444-52.
2 Rio J, Nos C, Tintore M, Tellez N, Galan I, Pelayo R, Comabella M,
Montalban X. Defining the response to interferon-beta in relapsing-
remitting multiple sclerosis patients. Ann Neurol 2006; 59: 344-52.
3 AEs were within the established range as reported in the Betaseron PI.

Website: http://www.berlex.com/

Resveratrol Studies Suggest Broad Implications for SIRT1 Activation in Neurodegenerative Eye Disorders

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jul 31, 2007 - Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that activation of SIRT1, a member of the sirtuin family of enzymes, was shown to be neuroprotective in an animal model of optic neuritis. These findings appear in an article published in Volume 48, Number 8 of The Investigative Ophthalmology and Visual Science Journal (IOVS), Shindler et al., 2007 entitled "SIRT1 Activation Confers Neuroprotection in Experimental Optic Neuritis."

The progressive loss of neurons with age may underlie a variety of debilitating neurological disorders including optic neuritis, one of the first signs of multiple sclerosis, which has been associated with reduced mitochondrial function. Sirtuins are a recently discovered class of enzymes that appear to affect the aging process in mammals and increase the number and function of mitochondria.

According to the findings in this paper, resveratrol, a SIRT1 activator reduced the loss of retinal ganglion cells and preserved axonal function in a pre-clinical model of optic neuritis. A single intravitreal dose of SRT501, Sirtris' proprietary formulation of resveratrol, was sufficient for neuroprotection. Furthermore, this neuroprotective effect was shown to be SIRT1 dependent because it was blocked by sirtinol, a SIRT1 inhibitor.

The authors of the IOVS article include Sirtris Pharmaceuticals, Inc. Senior Vice President, Head of Development, Peter Elliott, Ph.D. and Sirtris Scientific Advisory Board member, Kenneth Shindler, M.D., F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania.

"This work is significant because it shows that a SIRT1 activator is neuroprotective and thus has the potential to be therapeutic for a range of neurodegenerative diseases of aging," said Peter Elliott, Ph.D.

Christoph Westphal, M.D., Ph.D., Chief Executive Officer of Sirtris Pharmaceuticals, Inc. added, "These new data support our belief in SIRT1 as a therapeutic target for a broad range of diseases of aging including metabolic, mitochondrial, and neurological disorders."

Online copies of the article can be obtained at: http://www.iovs.org

About Sirtris Pharmaceuticals

Sirtris Pharmaceuticals is a biopharmaceutical company focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Our drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that control the aging process. The company's headquarters are in Cambridge, Massachusetts.

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, the potential therapeutic effects of SIRT1 activators for multiple neurodegenerative diseases and other types of disorders, the progress and results of pre-clinical studies of SIRT1 activators, and the potential of sirtuin modulators to receive regulatory approval. These forward-looking statements about future expectations, plans and prospects of Sirtris Pharmaceuticals involve significant risks, uncertainties and assumptions, including risks related to the lack of results that would provide a basis for predicting whether any of the Company's product candidates will be safe or effective, or receive regulatory approval, the possibility that results of pre-clinical studies are not necessarily predictive of clinical trial results, the Company's potential inability to initiate and complete pre-clinical studies and clinical trials for its product candidates, the fact that none of the Company's product candidates has received regulatory approvals, the potential inability of the Company to gain market acceptance of the Company's product candidates, and those other risks factors that can be found in the Company's filings with the Securities and Exchange Commission. Actual results may differ materially from those Sirtris Pharmaceuticals contemplated by these forward-looking statements. Sirtris Pharmaceuticals does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.

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Accentia files preliminary IND for MS drug

1st August 2007
By Sarah Routledge

Accentia Biopharmaceuticals has filed a preliminary Investigational New Drug application with the FDA for Revimmune in the treatment of refractory multiple sclerosis.

The company has requested a meeting with the FDA within the next 60 days to discuss a proposed pivotal Phase III clinical trial involving approximately 270 patients with relapsing/remitting multiple sclerosis MS with a primary endpoint of improvement in function (reversal of disability).

Based on a clinical study at the Johns Hopkins University School of Medicine, which showed an unprecedented 42% average improvement in function, Accentia believes that Revimmune holds the potential to restore function in many patients who have acute deficits due to MS.

In addition, the company believes that the long-term follow-up with patients in the proposed 48-week trial will demonstrate that Revimmune induces not only a reduction of the risk of exacerbations, but potentially also long-lasting remissions and possibly cures in MS patients.

Revimmune temporarily eliminates peripheral immune cells, including the immune cells causing the autoimmunity, while selectively sparing hematopoeitic stem cells in the bone marrow. Investigators at Johns Hopkins discovered that stem cells uniquely have high levels of a particular protective enzyme that can be measured in advance of therapy, which makes them impervious to Revimmune, and allows the surviving stem cells to give rise to a new immune system over two to three weeks.

The newly reconstituted peripheral immune system typically lacks the misdirected immunity to self-antigens, which is characteristic of autoimmune diseases.

Research teams uncover risk genes for multiple sclerosis

01.08.2007

Two new large-scale genomic studies have honed in on the main genetic pathway associated with multiple sclerosis (MS), while also uncovering new genetic variations in the disease and suggesting a possible link between MS and other autoimmune diseases.

The first study, led by an international consortium of clinical scientists and genomics experts, incorporates the two largest collections of MS genetic information worldwide and is the first comprehensive study to investigate the overall genetic basis of MS. Its findings appear in the July 29, 2007 online edition of the “New England Journal of Medicine”.

Another study is being published simultaneously on the web site of “Nature Genetics,” and focuses on one variant in a gene called interleukin-7 receptor (IL-7R), which researchers had thought was connected to the disease and now know increases the risk of MS.

“Scientists have known for 30 years that genetics play a critical role in MS, but the disease is influenced by so many different factors that it has consistently eluded us,” said Stephen Hauser, MD, professor of neurology at the University of California, San Francisco and an author on both papers. “It wasn’t until we could map genomes and then combine the efforts of dozens of researchers, that we could put all the pieces together.”

Together, he said, these two papers illustrate how scientific collaboration and the recent breakthroughs in genomic technology, which make it possible to both screen an individual’s genetic architecture and understand the differences, can open up an age-old disease such as multiple sclerosis.

It is significant that the two studies used very different approaches, but both highlighted the role of IL-7R, he said.

“Together, these place the IL-7R pathway at the center of understanding MS pathogenesis,” Hauser said. “I believe that this receptor and its interaction with regulatory T cells will now become a major focus of research on MS.”

The NEJM paper involved a hypothesis-neutral approach, in which the research teams scanned the entire genome of MS patients, their families and a control group for similarities and differences. By contrast, the “Nature Genetics” paper hypothesized that IL-7R was significant and focused on that portion of the genome to assess whether it was, in fact, a key factor in the MS patients.

MS is a disease of the central nervous system whose symptoms range from mild muscle weakness to partial or complete paralysis. It is widely considered an autoimmune disease that arises from a combination of genetic and environmental factors. This collusion of events leads the body to attack and destroy the insulation along nerve fibers.

The consortium study, reported in NEJM, was co-led by researchers at UCSF and five other universities and medical centers in the United States and England. The team analyzed genomic information from 12,360 people and confirmed that immune system genes are altered in people diagnosed with MS. It also pointed to potential mechanisms of the disease.

This study analyzed single nucleotide polymorphisms (SNPs), which are small differences in the DNA sequence that represent the most common genetic variations between individuals. The team looked for variations that were more commonly inherited by people with MS compared to samples from people without the disease.

Until now, the only genetic link identified with MS was in the major histocompatibility complex (MHC), a large cluster of genes responsible for many immune functions, including preventing the body’s immune cells from attacking its own tissues. This analysis confirmed that link while also finding other variants in genetic regions that are more common in people with MS.

“Scientists are increasingly finding genetic links between autoimmune diseases that affect different tissues in the body, including type 1 diabetes and rheumatoid arthritis,” said David Hafler, MD, the Jack, Sadie and David Breakstone professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, another of the consortium study authors. “This study will likely spur further research into the connection between these seemingly separate conditions.”

These advances are an outgrowth of a 15-year effort at UCSF to create a national repository of more than 10,000 samples of DNA from people with MS and their families, the largest such collection nationwide. A similar database, in both quantity and quality, had been developed at the University of Cambridge, in England. Both collections were used for both of these studies.

But the real breakthroughs came through collaboration. Hauser said that individually, none of the six centers in the consortium could have completed a study of this scale and complexity, but by using a Collaborative Research Award from the National MS Society, they were able to form a truly effective international consortium that could deliver the most exhaustive search for MS risk factors ever published.

The consortium paper is among a series of recent whole-genome association studies that have begun to uncover the genetic basis of complex diseases like diabetes, schizophrenia, and coronary artery disease. Unlike diseases caused by a mutation in a single gene, these conditions seem to arise from a combination of genetic, behavioral and environmental factors.

Jorge Oksenberg, PhD, a UCSF neurology professor who has been involved in the development of the UCSF collection for more than a decade, said that it wasn’t until scientists were able to combine the potential of both repositories with the intellectual and financial resources of previously competing research teams that they were able to make the connections represented in these studies.

“For studying these complex genetic diseases, where we’re looking at many genes contributing and each one contributing just a little bit, we need a very large group of patients and controls,” said Oksenberg, who, along with Hauser, worked on both the consortium research and the study for the “Nature Genetics” paper. “We’re looking for genetic markers that we know are common in the population at large, but they’re somehow more common in the MS patients, and when combined, they make the patient more susceptible to getting MS.”

Genomic technologies have now made it possible to uncover these subtle genetic associations. The next step is to begin to collect larger numbers of samples and examine more DNA sequences, which will allow scientists to identify subtler variations that contribute to the disease.

“Despite all the hype and new technology, the genome is still mysterious to us,” Oksenberg said. “This has opened a new window into MS genetics. Now we need to understand what these chains are doing.”

The international collaboration is currently planning even larger and more detailed explorations of the genetic landscape of MS and is now committed to making the entire data set available to MS researchers worldwide.

Kristen Bole | Source: EurekAlert!
Further information: www.ucsf.edu