Pluristem's PLX Cells Show a Statistically Significant Advantage in a Pre-Clinical Study in the Multiple Sclerosis Model

2008-04-14 20:16:34 -

Pluristem Therapeutics Inc. (NASDAQ:PSTI) (DAX:PJT) a bio-therapeutics company dedicated to the commercialization of non-personalized (allogeneic) cell therapy products for a variety of degenerative, ischemic and autoimmune indications, announced today that a preclinical study utilizing the Company's PLacental eXpanded (PLX) cells showed a statistically significant advantage in ameliorating functional deficiencies in a standard Multiple Sclerosis (MS) animal model. PLX cells are mesenchymal stromal cells (MSCs) obtained from the placenta and expanded using Pluristem's proprietary 3D PluriX(TM) technology.

Researchers at Pluristem utilized the Experimental Autoimmune Encephalitis (EAE) animal model for the study, the paradigm for MS in humans. After EAE was induced, a number of the animals were given PLX cells intravenously while the remaining served as a control. There was a significant reduction in the EAE score in those animals given PLX cells versus the control group and this beneficial effect was seen throughout the 25-day duration of the study. The EAE score is a measurement of functional outcomes in the EAE-afflicted animal and correlates closely with a histological improvement in EAE-induced lesions. Additionally, the beneficial effects were similar to when Zappia et. al. used MSCs that were non-placental in origin in this EAE animal model(1).

Zami Aberman, Pluristem's President and CEO said: "We are very excited that our PLX cells were able to demonstrate beneficial results that are statistically significant in this standardized model for Multiple Sclerosis. These results, in addition to our previously announced PLX STROKE results, demonstrate that PLX cells may be useful in the treatment of central nervous system (CNS) disorders and potentially help millions of people. Additionally, we believe this experiment demonstrates we can potentially utilize our off-the-shelf, easy to obtain PLX cells and achieve results that are as good as or better than MSCs obtained from other more difficult to find sources."

(1)Zappia et. al. Mesenchymal stem cells ameliorate experimental autoimmune encephalitis inducing T cell anergy. Blood. 2005;106: 1755-1761

About Multiple Sclerosis (MS)

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination. Myelin is the insulating sheath that surrounds nerve cells (neurons). MS may cause numerous physical and mental symptoms, and often progresses to physical and cognitive disability. The World Health Organization (WHO) estimates that over 2.5 million people globally suffer from MS, which represents a current market of approximately $5.4 billion for disease-modifying agents to treat the disorder.

About Pluristem

Pluristem Therapeutics Inc. is a bio-therapeutics company dedicated to the commercialization of non-personalized (allogeneic) cell therapy products for the treatment of several severe degenerative, ischemic and autoimmune disorders. The Company is developing a pipeline of products, stored ready-to-use, that are derived from the human placenta, a non-controversial, non-embryonic, adult stem cell source.

These placental mesenchymal stromal cells (MSCs) are expanded in the Company's proprietary PluriX(TM) 3D bioreactor, which imitates the natural microstructure of bone marrow and does not require supplemental growth factors or other exogenous materials. Pluristem believes the resultant PLX (PLacental eXpanded) cells are multi-potent and able to differentiate into a variety of cell types. Recent evidence also suggests their efficacy may be related to the secretion of cytokines or other potent immune modulators. Furthermore, PLX cells are immune privileged and have immunomodulatory properties, thus protecting the recipient from immunological reactions that often accompany transplantations.

Pluristem's first product, PLX-PAD, is intended to improve the quality of life of millions of people suffering from peripheral artery disease (PAD). The Company's PLX-I product is intended to resolve the global shortfall of matched tissue for bone marrow transplantation (BMT) by improving the engraftment of hematopoietic stem cells (HSCs) contained in umbilical cord blood (UCB). PLX-STROKE shows potential to become a new treatment for the functional recovery from an ischemic stroke.

Pluristem has offices in the USA with research and manufacturing facilities in Israel. www.pluristem.com

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Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and federal securities laws. These forward-looking statements are based on the current expectations of the management of Pluristem only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. For example, when we say that the Company's PLacental eXpanded (PLX) cells showed a statistically significant advantage in ameliorating functional deficiencies in a standard Multiple Sclerosis (MS) animal model; that these results, in addition to our previously announced PLX STROKE results, demonstrate that PLX cells may be useful in the treatment of central nervous system (CNS) disorders and potentially help millions of people; that we believe this experiment demonstrates we can potentially utilize our off-the-shelf, easy to obtain PLX cells and achieve results that are as good as or better than MSCs obtained from other more difficult to find sources, we are using forward looking statements. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; we may be unable to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties may develop with our process; results in the laboratory may not translate to equally good results in real surgical settings; our patents may not be sufficient; our products may harm recipients; changes in legislation; inability to timely develop and introduce new technologies, products and applications; loss of market share and pressure on pricing resulting from competition, which could cause the actual results or performance of Pluristem to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, Pluristem undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risk and uncertainties affecting Pluristem, reference is made to Pluristem's reports filed from time to time with the Securities and Exchange Commission.

Pluristem Therapeutics Inc.
Investor Contact:
William Prather RPh, MD, Sr. VP Corporate Development
303-883-4954
bill@pluristem.com

Positive Results Published On Testosterone For Men With MS

Researchers from the University of California, Los Angeles have published results from a small study, funded by the National MS Society and others, suggesting that one year of treatment with a gel containing the sex hormone testosterone (applied to the skin) in 10 men with relapsing-remitting multiple sclerosis resulted in significant improvements in cognitive function and in slowing brain tissue loss. Nancy Sicotte, MD, Rhonda Voskuhl, MD, and colleagues report these positive findings in the May 2007 issue of Archives of Neurology (2007;64:683-688 ).

Further research involving larger numbers of patients and controls would help to confirm and expand these early results, and to ensure the safety and effectiveness of testosterone treatment in MS.

Background: Sex hormones may contribute to MS susceptibility by influencing the immune attack on brain and spinal cord tissues. Laboratory studies have shown that the severity of EAE, an MS-like disease, is decreased when testosterone, a male sex hormone, is administered to male and female mice. Dr. Voskuhl was awarded funding from the National MS Society's targeted research initiative on Gender Differences in MS to undertake a small study of testosterone gel in men with MS. Preliminary results of this study were originally presented at the 58th Annual Meeting of the American Academy of Neurology in April 2006.

Study: Ten men with relapsing-remitting MS, ranging from 29 to 61 years of age, were studied. Relapsing-remitting MS is the most common form of the disease, involving clearly defined flare-ups followed by partial or complete recovery periods. After a six-month observation period, they were treated with testosterone gel applied to the skin (10 grams daily, containing 100 mgs of testosterone) for one year. None of the men were taking disease-modifying therapies. Clinical assessments including blood tests, as well as clinical measures of disease activity and cognitive function were completed every three months. Magnetic resonance imaging scans were taken before treatment and monthly to measure evidence of disease activity. The extent of brain tissue loss (atrophy) was assessed by determining normalized brain volumes using automated computer software.

Since all 10 of the men received treatment and none received inactive placebo, the investigators compared measures taken before treatment versus after treatment. Testosterone levels were in the lower range of normal before treatment, and although they increased with treatment, remained in the normal range.

After 12 months of testosterone treatment, measures of clinical disease activity remained stable, blood tests were normal, and no adverse events related to treatment were reported. The men showed significant improvements in performance on a test of cognitive function called the Paced Auditory Serial Addition Task (a test of processing speed and memory) compared to the pre-treatment period. The authors report that the improvement could not be accounted for by well-known "practice effects," which had stabilized during the pre-treatment period.

MRI scans showed no increases in disease activity or tissue damage during treatment, although the authors note that the patients began the study with relatively low levels of disease activity on MRI.

Significantly, the rates of brain atrophy, measured by normalized brain volume, slowed by 67 percent during the last nine months of treatment. Muscle mass increased significantly during the study; testosterone is sometimes used for this purpose in other chronic diseases.

This small study shows that testosterone treatment may have therapeutic benefit in men with relapsing-remitting MS. Further study involving larger numbers of patients and control groups is necessary to confirm these early results, and to ensure the safety and effectiveness of testosterone treatment for MS.

"We're gratified that these early, promising results stemmed from the National MS Society's targeting of gender differences as an important area of research in MS," said Dr. John R. Richert, the Society's executive vice president of research. "It also demonstrates how basic laboratory findings can quickly translate into possible new therapeutic strategies."

Dr. Voskuhl and colleagues are already proceeding with a similar effort involving the sex hormone estriol: Based on a small, early-phase trial that showed decreases in disease activity in 12 women with MS, she is now launching a multicenter, controlled clinical trial of oral estriol (added to the approved MS therapy glatiramer acetate) in 130 women with relapsing-remitting MS.

Jefferson Immunology Researchers Show Blood-brain Barrier Damage Could Affect MS Severity

Immunology researchers at the Kimmel Cancer Center at Jefferson studying a multiple sclerosis (MS)-like disease in mice have shown that the amount of "damage" to the central nervous system's protective blood-brain barrier - in essence, opening it - almost always correlates to the severity of the disease. The findings, reported online in the Proceedings of the National Academy of Sciences, can be used for testing potential MS therapies and for better understanding the role of the blood-brain barrier in disease processes.

Scientists led by D. Craig Hooper, Ph.D., associate professor of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Hilary Koprowski, M.D., professor of cancer biology at Jefferson Medical College and director of Jefferson's Center for Neurovirology and the Biotechnology Foundation Laboratories, wanted to find out what factors might affect the onset and severity of EAE (experimental allergic encephalomyelitis), an MS-like autoimmune disease often used as a model. They studied various strains of mice, each lacking some genes associated with inflammation and immunity, and looked at what happened to the blood-brain barrier.

They discovered that the amount of blood-brain barrier damage and subsequent permeability increase correlated to the severity of disease, and surprisingly, in nearly every case, the mouse's genetic make-up didn't matter. The mice developed EAE even without supposedly crucial factors in inflammation and autoimmunity - and disease.

"We've now shown in all of these mice missing certain components of the immune system that, as expected, opening the blood-brain barrier and letting cells and factors in from the circulation is critical to the development of disease," Dr. Hooper says. "The fact that the extent of the permeability change correlates with the severity of clinical disease signs shows that this is an important element in determining how sick these animals can get.

"This puts an emphasis on the fact that blood brain permeability changes are an important aspect of the development of a CNS inflammatory disease like EAE, an animal model of MS," he says.

According to Dr. Hooper, previous studies by his group and other researchers have shown that blood-brain barrier permeability is critical in the development of MS. To study this permeability, he and his co-workers looked at a range of mice lacking certain genes for various types of immune system and inflammatory cells such as NF kappaB, TNF-alpha, and interferon alpha, beta and gamma that contribute to disease. The researchers established EAE in each mouse strain and examined what was common to all of the animals when they developed disease.

"What's astounding is that mice that wouldn't be expected to develop EAE because they have major defects in their immune system are still able to develop disease," though at different rates, he notes.

However, mice missing the immune protein TNF-alpha often did not show disease, despite the increase in brain barrier permeability, causing the scientists to speculate about its role in the disease. "This is the first proof that there are permeability changes in all of these animals and the first hint that permeability doesn't always equal disease," he says.

Dr. Hooper notes that the work is part of the long-range goal of determining the exact role of blood-brain barrier permeability in disease. "These results tell us a great deal about the mechanisms that damage the blood-brain barrier," he says. "All of these factors that are missing in the mice aren't essential to opening the blood brain barrier."

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Contact: Steve Benowitz
Thomas Jefferson University