Telomeres, structures that cap the ends of cells’ chromosomes, grow shorter with each round of cell division unless a specialized enzyme replenishes them. Maintaining telomeres is thought to be important for healthy aging and cancer prevention.

By this measure, T cells, or white blood cells, from patients with the autoimmune disease rheumatoid arthritis are worn out and prematurely aged, scientists at Emory University School of Medicine have discovered.

Compared with cells from healthy people, T cells from patients with rheumatoid arthritis have trouble turning on the enzyme that replenishes telomeres, they found. Reversing this defect could possibly help people prone to the disease maintain a balanced immune system.

The results are published online this week in Proceedings of the National Academy of Sciences.

In rheumatoid arthritis, T cells are chronically over-stimulated, invading the tissue of the joints and causing painful inflammation. This derangement can be seen as a result of the loss of the immune system’s ability to discriminate friend from foe, says senior author Cornelia Weyand, MD, PhD, co-director of the Kathleen B. and Mason I. Lowance Center for Human Immunology at Emory University.

In childhood, new T cells are continually produced in the thymus, she says. But after about age 40, the thymus “involutes” – or shrinks and ceases to function. After that, the immune system has to make do with the pool of T cells it already has.

“What we see in rheumatoid arthritis is an aged and more restricted T cell repertoire,” she says. “This biases the immune system toward autoimmunity.”

Weyand, postdoctoral fellow Hiroshi Fujii, MD, PhD, and their colleagues were interested in mechanisms of T cells’ premature aging, because scientists had previously observed that in rheumatoid arthritis, T cells tend to shift the molecules on their surface and function differently.

They found the answer in telomerase, the enzyme that renews telomeres and is necessary to prevent loss of genetic information after repeated cell division.

Telomerase adds short repeated DNA sequences to the ends of chromosomes to protect them. The enzyme is active in embryonic development but is usually switched off in adult cells. Many cancer cells reactivate it to enable runaway growth.

T cells are some of the very few cells in adults that can turn on telomerase when stimulated, probably because they have to divide many times and stay alive for decades.

Weyand and Fujii found that T cells from patients with rheumatoid arthritis make 40 percent less telomerase enzyme when stimulated. The cells came from 69 patients, 92 percent female, with an average age of 50, and were compared with cells from healthy people with similar demographics.

Shutting off a gene encoding part of the enzyme made normal T cells vulnerable to programmed cell death, and transferring telomerase into patients’ T cells rescued them from dying.

The finding suggests that restoring defective telomerase to T cells could possibly help “reset” the immune system in rheumatoid arthritis, Weyand says.

Pharmaceutical industry researchers have been looking for drugs that could elevate or depress telomerase activity, with the goal of either prolonging life or treating cancer. However, turning on telomerase indiscriminately could lead to cancer, so any treatment would have to be targeted to the right cells, she says.

Notes:

The research was funded by the National Institutes of Health and the Diane Wolf Discovery Fund.

Fujii is now an assistant professor of hematology and rheumatology at Tohoku University School of Medicine in Japan.

Reference: H. Fujii, L. Shao, I. Colmegna, J. Goronzy and C.M. Weyand. Telomerase insufficiency in rheumatoid arthritis. http://www.pnas.org/cgi/doi/10.1073/pnas.0811332106

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing and public health; the Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX) today announced that it has submitted a clinical trial application (CTA) to initiate a phase 1 trial using the HuCAL-derived antibody MOR103 for the treatment of Rheumatoid Arthritis. MorphoSys plans to reveal the target molecule of its lead antibody program MOR103 and additional information on the design of the phase 1 clinical study on January 16, 2008.

“The initiation of clinical development of our lead proprietary drug candidate MOR103 is a significant milestone for MorphoSys and we achieved it as planned by the end of 2007. We look forward to providing an in-depth update on MOR103 in January,” commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG.

MorphoSys will hold a public conference call and live audio webcast on January 16, 2008 to provide detailed information on its lead compound MOR103. Additional information will be provided on the Company’s website: www.morphosys.com/conferencecalls

About MorphoSys

MorphoSys is a publicly traded biotechnology company focused on the generation of fully human antibodies as a means to discover and develop innovative antibody-based drugs against life-threatening diseases. MorphoSys’s goal is to establish HuCAL as the technology of choice for antibody generation in research, diagnostics and therapeutic applications. The Company currently has therapeutic and research alliances with the majority of the world largest pharmaceutical companies including Bayer-Schering, Boehringer Ingelheim, Centocor/Johnson & Johnson, Novartis, Pfizer and Roche. Within these partnerships, more than 40 therapeutic antibody programs are ongoing in which MorphoSys participates through exclusive license and milestones payments as well as royalties on any end products. Additionally, MorphoSys is active in the antibody research market through its AbD Serotec business unit. The business unit has operations in Germany (Munich), the U.S. (Raleigh, NC) and U.K. (Oxford). For further information please visit www.morphosys.com

HuCAL(R) and HuCAL GOLD(R) are registered trademarks of MorphoSys AG

This communication contains certain forward-looking statements concerning the MorphoSys group of companies. The forward-looking statements contained herein represent the judgment of MorphoSys as of the date of this release and involve risks and uncertainties. Should actual conditions differ from the Company’s assumptions, actual results and actions may differ from those anticipated. MorphoSys does not intend to update any of these forward-looking statements as far as the wording of the relevant press release is concerned.

The Arthritis Foundation, the leading health organization addressing the needs of 46 million Americans living with arthritis, announced that Amgen and Wyeth Pharmaceuticals, co-marketers of Enbrel® (etanercept), will be the national presenting sponsor of the 2008 Arthritis Walk®.

“The Arthritis Foundation hosts hundreds of Arthritis Walk events nationwide to raise funds to prevent, control and cure arthritis, the nation’s most common cause of disability,” said Becky Burkett, chief development officer of the Arthritis Foundation. “This generous sponsorship from Amgen and Wyeth will provide a unique opportunity to generate awareness about arthritis while raising funds that are critical to helping find a cure for this debilitating condition.”

As part of the sponsorship, the Arthritis Foundation will launch a new program in which the organization will reach out to rheumatologists and members of the Association of Rheumatology Health Professionals in an effort to help boost attendance and awareness of the Arthritis Walk by encouraging doctors and their patients to walk together.

“We’re excited to have the opportunity to support a program that benefits the entire arthritis community,” said Jeffrey M. Melin, M.D., M.P.H., senior director, Musculoskeletal and Inflammatory Diseases, Wyeth Research. “We encourage people with arthritis to join the Arthritis Walk together with their doctor, as well as their friends and family, and to take an active role in improving their own health, while raising awareness and funding for arthritis research.”

“Arthritis can pose challenges to physical activity, but it does not have to mean the end of an active and healthy lifestyle,” said Scott Baumgartner, M.D., director, Global Development, Inflammation Therapeutic Area, Amgen. “We hope that together with the Arthritis Foundation we can empower and motivate people with rheumatoid arthritis to consult with their rheumatologist and start or restart an appropriate fitness program.”

Arthritis Walk events, which take place nationwide, kick off National Arthritis Month in May. Walking as little as 30 minutes – even 10 minutes three times a day – can be beneficial for everyone and may ease joint pain and improve mobility. For people with arthritis, experts believe that light exercise such as walking may decrease fatigue, strengthen bones and muscles, and enhance flexibility and stamina. To sign up for an Arthritis Walk event, visit www.arthritis.org.

While often referred to as if it were a single disease, arthritis is actually an umbrella term used for a group of more than 100 medical conditions that collectively affect the joints of nearly 46 million adults and 300,000 children in America alone. Osteoarthritis, the most common form of arthritis, is most prevalent in people over 60 years of age, while rheumatoid arthritis appears primarily in women in their young- to mid-adult years. Juvenile rheumatoid arthritis is the most common form of arthritis in children.

About the Arthritis Foundation

The Arthritis Foundation is the leading health organization addressing the needs of some 46 million Americans living with arthritis, the nation’s most common cause of disability. Founded in 1948, with headquarters in Atlanta, the Arthritis Foundation has multiple service points located throughout the country.

The Arthritis Foundation is the largest private, not-for-profit contributor to arthritis research in the world, funding more than $380 million in research grants since 1948. The foundation helps individuals take control of arthritis by providing public health education; pursuing public policy and legislation; and conducting evidence-based programs to improve the quality of life for those living with arthritis.

http://www.arthritis.org

About Amgen and Wyeth

Amgen and Wyeth Pharmaceuticals, a division of Wyeth, market ENBREL in North America. Wyeth markets ENBREL outside of North America. Immunex Corporation, a wholly owned subsidiary of Amgen, manufactures ENBREL, which may be used to treat rheumatoid arthritis, junior rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and psoriasis. Additional information about ENBREL, including the full U.S. Prescribing Information, can be found on the Web site sponsored by the companies at http://www.enbrel.com.

Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about Amgen’s pioneering science and vital medicines, visit http://www.amgen.com.

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women’s health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products. Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

Wyeth Pharmaceuticals

Affecting more than 10 million Americans, Osteoarthritis of the knee (OA) is one of the five leading causes of disability among the elderly. While OA mainly affects most people over 45, it can occur at any age. A double-blind, placebo-controlled study published in the journal Nutrition Research reveals Pycnogenol, (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, improved physical function by 52 percent in patients suffering from OA.

When OA develops, the cartilage gradually looses elasticity and begins to harden and crack, subsequently becoming more prone to damage and erosion by use or injury and often leads to pain, swelling, a decrease in motion at the joint, stiffness, or the formation of bone spurs (tiny growths of new bone). Current treatments include regular exercise and pain relievers such as NSAIDS and COX-2 inhibitor pills to help ease pain and stiffness. In more severe cases, cortisone shots can help decrease inflammation in the joint and extreme cases consist of joint replacement. There are currently no drugs that treat osteoarthritis directly.

Pycnogenol was chosen due to a history of studies of the extract to alleviate inflammation by inhibiting COX-1, COX-2 and the pro-inflammatory “master-switch” nuclear factor-kappa B,”said lead researcher Dr. Ronald Watson from the University of Arizona. Pycnogenol offers a safe nutritional approach to significantly reduce pain and improve physical function of arthritic joints. It controls inflammation and thus ideally complements existing strategies that comprise delivery of building blocks for replacement of degenerated cartilage.

The study was conducted at the rheumatology department of Mashhad Medical University, Iran. Thirty-five volunteers (average age 42) were randomly assigned a daily dose of Pycnogenol (50mg, 3 times a day) or placebo for three months. Patients were to report arthritic pain using the Western Ontario and McMasters Universities (WOMAC) Osteoarthritis Index after 30, 60 and 90 days. Participants also were instructed to indicate the frequency and dosage of NSAIDS and COX-2 inhibitor usage.

After two months of supplementation, physical function and pain scores improved in the Pycnogenol group. After three months in the Pycnogenol group, there was a reduction of 43 percent in pain, 35 percent in stiffness, 52 percent in physical function subscales and 49 percent composite WOMAC. The placebo group showed no significant scores throughout the entire study. Additionally, further reduction in the number of NSAIDS and COX-2 inhibitor pills and number of days taking medication was noted in the Pycnogenol group.

Pycnogenol’s natural anti-inflammatory and antioxidant properties were responsible for delivering these excellent results,”said Watson. This study shows that supplementing with Pycnogenol can fight joint inflammation and soothe the pain and stiffness, thus pave the path for cartilage renewal with substances such as glucosamine.

A previous study on Pycnogenol published in the Journal of Inflammation demonstrated that the ingredient effectively prevented inflammation disorders in patients by moderating the immune system response. While the wear and tear is responsible for the initial degeneration of cartilage, the more advanced stage of osteoarthritis involves inflammation. The cells of the cartilage (chondrocytes) respond to mechanical impact by generating pro-inflammatory molecules (cytokines). This process is initiated by the pro-inflammatory “master-switch” called NF-kappaB. Pycnogenol was shown to lower the sensitivity for NF-kappaB in humans last year.

The cytokines released from chondrocytes recruits immune cells (leukocytes) to the joints where they cause more harm than good. Leukocytes release harmful substances such as free radicals and enzymes that break down connective tissue and speed up the degeneration of cartilage. These processes alike are under control by NF-kappaB, and the effect of Pycnogenol to suppress NF-kappaB will help to limit the damage caused by leukocytes.

Researchers believe this study is the first randomized clinical trial to show Pycnogenol’s effectiveness in alleviating the clinical symptoms of knee osteoarthritis. There are several more breakthrough studies on Pycnogenol and osteoarthritis expected to be published next year allowing for development of innovative, natural formulas for joint health.

Additionally, Horphag Research, the exclusive worldwide distributor of Pycnogenol has filed for several patents for Pycnogenol’s application for COX-1, COX-2 and treating osteoarthritis.

Total hip arthroplasty (THA), or hip replacement, is an effective treatment for osteoarthritis (OA), but most studies have only followed patients for up to one year. A new study published in the December issue of Arthritis Care & Research examined patients after an average of eight years following hip replacement and found a long-term positive impact on their physical functioning.

Led by Professor Cyrus Cooper and Ms. Janet Cushnaghan of the University of Southampton in Southampton, UK, the study included 282 patients from two English health districts who had OA and were placed on the waiting list for a hip replacement between 1993 and 1995. It also included 295 matched controls from the general population. At the start of the study patients were interviewed about hip injury, pain, physical function, vitality and mental health. In addition, their BMI was calculated, their hands were examined for Heberden’s nodes, an indication of OA, and their hip X-rays were evaluated for severity of OA. Between 2001 and 2004, they completed a self-administered questionnaire asking if and when they had undergone hip replacement, as well as questions about their physical function, vitality and mental health. Follow-up of the patients took place an average of eight years following hip replacement.

The results showed that patients who were waiting for a hip replacement had markedly worse physical functioning than the controls but only small differences in vitality and mental health at the start of the study. By the time of the follow-up, the physical functioning of the OA patients had improved (while that of the controls had deteriorated) but their vitality had deteriorated. In addition, better physical functioning at the start of the study was associated with a greater decline at follow-up, but higher BMI seemed to have no impact. Those with more severe OA according to their X-rays showed the most improvement in physical functioning.

“Our findings are consistent with a sustained beneficial impact on physical functioning following THA for OA, but we found no evidence for parallel improvement in vitality or mental health,” Professor Cooper stated. The researchers noted that the study is limited because it was an observational investigation as opposed to a randomized controlled trial and information about the patients’ disease and surgical procedures was limited. But this weakness was offset by the fact that the study had a long follow-up interval and a relatively large number of patients and controls. “Even when allowance is made for possible confounding effects, the long-term improvement in the physical functioning of the cases is striking when set against the decline that occurred in controls,” the authors note, suggesting that the benefits of hip replacement are substantial and long-lasting.

Although some previous studies have suggested that hip replacement benefits mental health as well, the current study did not find this to be the case, possibly because the mental health status of the patients at the beginning of the study was no different from the control group, even though they had greater physical limitations. Regarding the finding that BMI did not affect long-term physical functioning, the authors suggest that surgeons are perhaps careful in selecting obese patients for this procedure, but in any case a BMI in the range of up to 30 should not be a deterrent to hip replacement as long as the patient is healthy enough to undergo surgery.

The authors conclude that the study adds to the accumulating evidence of the long-term benefits of hip replacement, especially in patients with more severe changes seen on X-rays, and that perhaps these patients should be given higher priority for the procedure.

Two fibro-cartilaginous crescents, the menisci serve as cushions against joint cartilage degradation where the knee connects with the shin and thigh bones. Loss of meniscal function is recognized as a strong risk factor for knee osteoarthritis (OA). In the United States, about 6 percent of the over 30 through middle-age population and between 11 and 15 percent of senior citizens, age 65 and up, suffer from knee OA in form of frequent knee pain, aching, or stiffness. The prevalence of this routinely aggravating, often disabling condition is increasing. Associated with the toll of aging and obesity, as well as sports injuries, tears to the menisci are a common finding on magnetic resonance images, especially in the OA knee. However, whether meniscal damage foreshadows the development of knee pain in middle aged or elderly – or directly causes it – remains unknown.

Toward their goal of improving the early detection of knee OA, researchers with the Multicenter Osteoarthritis (MOST) Study set out to evaluate the effect of meniscal damage on the development of knee pain, aching, or stiffness in middle-aged and older adults. Based on their findings, featured in the December 2007 issue of Arthritis & Rheumatism, meniscal damage does often not directly provoke knee symptoms. “Any association between meniscal damage and frequent knee pain seems to be present because both pain and meniscal damage are related to OA,” notes study spokesperson Dr. Martin Englund of Boston University School of Medicine, “and not because of a direct link between the two.”

Researchers began by focusing on 3,026 individuals between the ages of 50 and 79, who either had signs of knee OA or were at a high risk of developing it. Recruited from two U.S. communities – Birmingham, Alabama, and Iowa, City – participants included men and women, whites and ethnic minorities. Based on telephone interviews and clinical visits with members of the study population, 110 case knees were identified. They were defined as knees free from symptoms at baseline, which had developed frequent pain, aching, or stiffness at the study’s 15-month culmination mark. 220 control knees were drawn randomly from those knees with no frequent symptoms at baseline that did not become cases.

Magnetic resonance imaging (MRI), trusted for its high sensitivity to detecting tissue and cartilage changes, was performed on case and control knees at baseline and at 15 months. Then, 2 musculoskeletal radiologists blinded to the case-control status of its subject assessed each film for meniscal damage using the following scale: 0 = intact, 1 = minor tear, 2 = non-displaced tear or surgical repair, and 3 = displaced tear, resection, maceration, or destruction. Finally, the effect of meniscal damage on the development of frequent knee pain, aching, or stiffness was analyzed by contingency tables and logistic regression.

At baseline, meniscal damage was detected on 38 percent of case knees and 29 percent of control knees. As expected, meniscal damage was more frequent in knees in which previous surgery or serious injury had been reported. Although there was a modest association between meniscal damage score and the development of frequent knee pain, aching, and stiffness after adjusting for age, sex, and body mass index – meniscal damage was mostly present and pronounced in knees with radiographic evidence of OA.

When considering the co-occurrence of OA and performing a stratified analysis, researchers found no independent association between meniscal damage and the development of frequent knee symptoms. “Meniscal damage in older adults is highly associated with OA of the knee,” Dr. Englund makes clear. “However, meniscal damage often seems not to be directly responsible for later symptoms, while other features of OA may be so.” Stressing the importance of treating OA as a whole-joint disorder, this study calls attention to the risk of misinterpreting meniscal damage as the direct cause of knee pain. As Dr. Englund acknowledges, it also emphasizes the need for further research into the possible role of different types and sites of meniscal damage in contributing to knee pain.

Osteoarthritis (OA) of the hip is a growing problem that will continue to increase as the population ages. Previous studies have reported on risk factors for developing OA, but few have examined the factors that might predict its prognosis. A new study published in the December issue of Arthritis Care & Research examined patients with hip pain to determine their disease progression and to find out how many underwent total hip replacement (THR) over the course of several years.

Led by Sita M.A. Bierma-Zeinstra and Annet M. Lievense of Erasmus Medical Center, Rotterdam, The Netherlands, the study included 227 patients who visited their general practitioners in 1996 because of hip pain. Patients were questioned about the severity of their hip pain and their general health, underwent a physical exam, had X-rays of the pelvic area and sonograms of the hip area. Three years later, the same patients underwent follow-up, during which they were interviewed in person about the progression of their hip pain and whether or not they received a THR. In addition, their OA was assessed using the WOMAC Osteoarthritis Index. After another three years, a comparable follow-up was carried out using a survey that was mailed to the patients.

The results showed that after three years, 12 percent of the patients underwent a THR because of severe pain and/or disability due to hip OA. After six years, this number increased to 36 percent. In addition, another 3 percent to 5 percent had severe pain or disability due to the condition. Being at least 60 years old, morning stiffness, pain in the groin, restricted extension and painful rotation of the hip joint were all associated with an increased risk for undergoing THR.

The researchers note that while an earlier analysis of their data did not indicate an association between age and progression of hip pain, the current study did find the two were connected. “The difference might be attributed to selection for surgery: if a patient is relatively young, physicians tend to postpone surgery to avoid the risk of re-surgery after 10-20 years,” the authors point out. Earlier studies reported a connection between baseline hip pain and progression of OA, but the current study did not find this to be the case. The authors suggest this may be because all of the patients in their study already had hip pain. Also, obese patients tended to have a decreased risk of THR after three years, which may be attributable to the fact that these patients are typically advised to lose weight before undergoing the surgery.

“With information obtained from history taking, physical examination, and radiology, we are now better able to identify persons who are at high risk for progression of hip OA,” the authors conclude. “This can be helpful not only to inform patients more precisely about the course of their hip pain, but also for future clinical trials.”

Osiris Therapeutics, Inc. (NASDAQ:OSIR) announced positive one-year interim results in the evaluation of Chondrogen, a preparation of adult stem cells formulated for direct injection into the knee. The one year data showed improvement in joint condition that correlated with a clinically and statistically significant improvement in pain in patients with osteoarthritis (OA) who received Chondrogen as compared to those treated with the control, hyaluronic acid (HA).

Key Points from the Trial

- OA patients receiving Chondrogen experienced a statistically significant reduction in pain as compared to those receiving the control, HA.

- The magnitude of improvement in pain was clinically significant and superior to the improvement reported for other approved treatments.

- Patients receiving the control were 3.5 times more likely to experience degenerative bone changes associated with OA as compared to those receiving Chondrogen.

- The effects were dose dependent and pain scores improved from six months to one year following treatment, suggesting Chondrogen caused a biological modification of OA.

- Chondrogen was well tolerated at both dose levels and there were no serious events associated with administration

“These results are very promising given that a single injection of Chondrogen resulted in a clinically significant reduction in pain that was about double what we typically achieve with products currently available for OA,” said C. Thomas Vangsness Jr., M.D., Professor of Orthopedic Surgery and Chief of Sports Medicine with the Keck School of Medicine at the University of Southern California. “These data have added significance given that superiority was observed over the control arm in this trial, HA, which is routinely used today for the treatment of osteoarthritis.”

The Phase I/II double-blind, controlled study of 55 patients is evaluating the safety and exploratory effectiveness of Chondrogen in patients undergoing surgery to remove a torn meniscus. In patients with OA at the time of surgery, a statistically significant 20 mm reduction in pain, as measured by the visual analog scale (VAS), was observed in patients receiving a single injection of Chondrogen over patients receiving an injection of the control, HA, at one year (Chondrogen 48 mm vs. Control 28 mm, p=0.05). The reduction in pain increased even further to 37 mm with more severe osteoarthritic changes in the patient’s joint (p=0.004, Chondrogen 56 mm vs. Control 19 mm). For comparison, currently available treatments for OA, such as HA which requires multiple injections, were approved by the Food and Drug Administration (FDA) based upon improvements of 9-23 mm over placebo.

There was also a positive dose-response effect. At one year, the improvement in pain relative to baseline, prior to surgery to remove damaged meniscus, was 56 mm for high dose Chondrogen, 26 mm for low dose Chondrogen, and 19 mm for the control.

“We are excited about the dramatic improvements seen in this trial, which offer hope to the 21 million Americans who suffer every day from the debilitating effects of osteoarthritis. Additionally, the durability of the effect may have a profound impact on cost of treating arthritis,” said C. Randal Mills, Ph.D., President and CEO of Osiris Therapeutics. “These data allow us to advance our development efforts with confidence. With both clinically and statistically significant results in an approvable endpoint, we have started preparing for the appropriate registration trials. I would like to thank the investigators and patients for their continued support with this landmark study.”

The beneficial effects of Chondrogen were also seen in physical measures of joint condition. Bony changes associated with osteoarthritis, such as subchrondral sclerosis and osteophyte formation, were reported in 21% of patients receiving the control, but only 6% of Chondrogen-treated patients. Joint condition was determined from MRI analysis using centralized, independent, blinded orthopedic radiologists.

“A major problem with OA is that our current treatments only provide patients with short-term relief. Chondrogen is the first product evaluated in humans with the ability to modify the biological processes associated with arthritis and therefore hold the promise of a lasting effect,” said Joel Boyd, M.D., an orthopedic surgeon at TRIA Orthopaedic Research Institute in Minneapolis, Minnesota, and a United States Olympic team physician. “The difference in improvement observed between patients receiving Chondrogen and HA continued to widen from six months to one year without the need for additional treatment. These results are consistent with the progressive nature of arthritis and support the preclinical data demonstrating Chondrogen can have a fundamental impact on the biological course of arthritis.”

In addition to the benefits observed in OA, Chondrogen continued to demonstrate a strong safety profile. Through one year there were no serious adverse events attributed to Chondrogen, and there was no evidence of abnormal tissue formation. One of the goals of the study was to assess the ability of MRI to detect the volume of meniscus regeneration following meniscectomy. The MRI volume analysis method was deemed unsuitable for computational analysis because of the high level of variability seen between readings. As a result, no meaningful evaluation of meniscus regeneration can be made.

About the Phase I/II Chondrogen Trial

The Phase I/II trial is a randomized, prospective, double-blinded trial, conducted at seven leading sports medicine centers in the US to assess the safety of an injection of stem cells into the joint capsule and to gain preliminary efficacy data on the ability of Chondrogen to impact tissue regeneration and the development of osteoarthritis. Patients in the study underwent standard meniscectomy surgery to remove torn or damaged tissue in their meniscus. One week following surgery, the patients were given a single injection of either HA or a low dose (50 million cells) or high dose (150 million cells) of Chondrogen. Neither the patients nor the surgeons know what was given for the duration of the study. Patients will be followed for safety and additional preliminary efficacy such as pain, cartilage damage, and tissue repair for two years under the current study protocol. Non-invasive MRI is being used for examination of meniscus and cartilage condition.

About Chondrogen

Chondrogen is a preparation of mesenchymal stem cells specifically formulated for direct injection into the knee. The stem cells are obtained from the bone marrow of healthy adult donors. Chondrogen is currently being evaluated in a double-blind, controlled Phase I/II study for the treatment of arthritis of the knee in the setting of meniscectomy.

About Osiris Therapeutics

Osiris Therapeutics, Inc. is a leading stem cell therapeutic company focused on developing and marketing products to treat medical conditions in the inflammatory, orthopedic and cardiovascular areas. Osiris currently markets and sells Osteocel® for regenerating bone in orthopedic indications. Prochymal™ is in Phase III clinical trials for both Graft versus Host Disease and Crohn’s disease and is the only stem cell therapeutic currently designated by FDA as both an Orphan Drug and Fast Track product. Osiris has also partnered with Genzyme Corporation to develop Prochymal™ as a medical countermeasure to nuclear terrorism and other radiological emergencies. The Company’s pipeline of internally developed biologic drug candidates under evaluation also includes Chondrogen™ for arthritis in the knee, and Provacel™, for repairing heart tissue following a heart attack. Osiris is a fully integrated company, having developed capabilities in research, development, manufacturing, marketing and distribution of stem cell products. Osiris has developed an extensive intellectual property portfolio to protect the company’s technology in the United States and a number of foreign countries including 47 U.S. and 215 foreign patents owned or licensed. More information can be found on the company’s website, http://www.Osiris.com. (OSIR-G)

Forward-Looking Statements

This press release contains forward-looking statements. Forward-looking statements include statements about our expectations, beliefs, plans, objectives, intentions, assumptions and other statements that are not historical facts. Words or phrases such as “anticipate,” “believe,” “continue,” “ongoing,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project” or similar words or phrases, or the negatives of those words or phrases, may identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. Examples of forward-looking statements include, but are not limited to, statements regarding the following: our product development efforts; our clinical trials and anticipated regulatory requirements; the success of our product candidates in development; status of the regulatory process for our biologic drug candidates; implementation of our corporate strategy; our financial performance; our product research and development activities and projected expenditures, including our anticipated timeline and clinical strategy for mesenchymal stem cells and biologic drug candidates; our cash needs; patents and proprietary rights; ability of our potential products to treat disease; our plans for sales and marketing; our plans regarding our facilities; types of regulatory frameworks we expect will be applicable to our potential products; and results of our scientific research.

Forward-looking statements are subject to known and unknown risks and uncertainties and are based on potentially inaccurate assumptions that could cause actual results to differ materially from those expected or implied by the forward-looking statements. Our actual results could differ materially from those anticipated in forward-looking statements for many reasons, including the factors described in the section entitled “Risk Factors” in our Annual Report on Form 10-K filed with the United States Securities and Exchange Commission. Accordingly, you should not unduly rely on these forward-looking statements. We undertake no obligation to publicly revise any forward-looking statement to reflect circumstances or events after the date of this press release or to reflect the occurrence of unanticipated events.

MedImmune, Inc. announced that dosing of patients has begun in the first Phase 1 clinical trial of CAM- 3001, a fully human monoclonal antibody (MAb) targeting the alpha subunit of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR). The study is designed to evaluate the safety and tolerability of single doses of CAM-3001 in patients with rheumatoid arthritis (RA), and represents the first clinical trial in which a MAb targeting GM-CSFR is being investigated in this population. MedImmune currently holds exclusive, worldwide rights to develop and market CAM-3001 under an agreement with CSL Limited.

“Commencing this trial demonstrates that researchers at MedImmune are at the forefront of innovation using monoclonal antibodies and evaluating their potential to serve as new treatment options for patients with chronic, debilitating inflammatory diseases, including rheumatoid arthritis,” said Ian Anderson, Ph.D., vice president of research — respiratory, inflammation and autoimmunity.

In MedImmune’s Phase 1, dose-escalation trial, patients will receive CAM- 3001 at Charite Research Organisation in Berlin, Germany across a range of escalating doses and will be monitored for up to seven months. Dose escalation will stop if maximum tolerated doses are reached.

CAM-3001, which was isolated and optimized at MedImmune’s Cambridge, UK facility using its innovative display platform, inhibits GM-CSF signaling, which has the potential for a significant anti-inflammatory effect. There is substantial evidence for a role of GM-CSF in RA. In preclinical studies, CAM- 3001 has demonstrated potent inhibition of GM-CSF mediated effects in a range of in-vitro and in-vivo assays relevant to RA. Additionally, elevated levels of GM-CSF and its receptor have been found in the joints of patients with RA. This provides a strong rationale for the potential use of CAM-3001 to treat this debilitating disease.

About MedImmune’s Anti-GM-CSFR Antibody Development Program

In 2001, MedImmune’s Cambridge facility (then known as Cambridge Antibody Technology) and AMRAD Operations Pty Ltd., now owned by CSL Limited, entered into a collaboration to jointly discover and develop human MAb therapeutics that neutralize the GM-CSF receptor, including CAM-3001. Under the terms of a subsequent licensing agreement entered into in August 2007, CSL will receive upfront and milestone payments, as well as royalties, on future sales of CAM- 3001. Additional terms of the agreement have not been disclosed.

About Rheumatoid Arthritis

Rheumatoid arthritis is a chronic systemic inflammatory disease that is associated with significant morbidity and mortality. The disease is characterized by inflammation of the synovial joints that can result in pain, swelling and joint damage with secondary deformity and progressive disability. Despite current treatment options, there is a significant mortality associated with RA, especially the more severe forms of the disease. There is need for additional treatments to control moderate to severely active disease. A new treatment is needed that may provide a significant clinical benefit for disease remission, as well as inhibiting progressive joint damage, and improving quality of life in patients with RA.

Actemra is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody seeking approval to treat rheumatoid arthritis

Roche announced the submission of a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval for Actemra (tocilizumab) to reduce the signs and symptoms in adults with moderate to severe rheumatoid arthritis (RA).

“The filing for Actemra in the U.S. is an important milestone for Roche, and brings us another step closer to making this therapy available to the millions of patients in the United States who suffer from the pain and debilitating effects of rheumatoid arthritis,” said William M. Burns, CEO of the Pharmaceuticals Division at Roche.

Actemra is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA. Research suggests that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, may reduce inflammation of the joints and relieve certain systemic effects of RA.

The BLA submission to the FDA is based on results from five international Phase III studies which demonstrated Actemra as monotherapy or in combination with disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate significantly reduced the signs and symptoms of rheumatoid arthritis, as measured by ACR and disease activity score (DAS) remission rates, compared with DMARD therapies alone. Furthermore, patients who had previously failed anti-tumor necrosis factor (anti-TNF) treatments also showed significant improvement in signs and symptoms of RA after treatment with Actemra.

The clinical development program conducted by Roche includes five clinical studies and has enrolled more than 4,000 patients in 40 countries, including the U.S. and Europe. One of these Phase III trials evaluating Actemra in RA is an ongoing two-year study and is expected to report one-year data evaluating the effect of Actemra on the inhibition of structural damage in 2008.

Roche will file a Marketing Authorisation Application (MAA) for the product with the European Medicines Agency (EMEA) in early December.

About Actemra

Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Actemra is the first humanised interleukin-6 (IL-6) receptor inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA, a disease with a high unmet medical need. The overall safety profile observed in the global studies of Actemra is consistent and Actemra is generally well tolerated. The serious adverse events reported in Actemra global clinical studies included serious infections and hypersensitivity reactions including a few cases of anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension. Increases in liver function tests (ALT and AST) were seen in some patients. These increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function.

Roche and Chugai are collaborating on a phase III clinical development programme in RA running outside Japan, with more than 4000 patients enrolled in 40 countries including several European countries and the USA. In Japan, Chugai launched Actemra in June 2005 as a therapy for Castleman’s disease and in April 2006 filed for the additional indications of rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.

About Roche in rheumatoid arthritis

One of the most important drivers for growth at Roche over the next few years is expected to be the company’s emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche’s second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6 , a protein that plays a major role in the RA inflammation process. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a humanised anti-CD20 antibody, has entered phase III development for RA.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. Additional information is available on the Internet at http://www.roche.com.

About Chugai

Chugai Pharmaceutical, specializes in prescription pharmaceuticals and based in Tokyo, is Japan’s leading research-based pharmaceutical companies with strengths in biotechnology products. Since the start of the strategic alliance with Roche in October 2002, Chugai is actively involved in prescription pharmaceutical R&D activities in Japan and abroad as an important member of the Roche Group. Specifically, Chugai is working to develop innovative products with global applications, focusing on the disease areas of oncology, renal disease, and bone and joint.

In Japan, Chugai’s research facilities in Gotemba and Kamakura are collaborating to develop new pharmaceuticals and Ukima is conducting research for technology development for industrial production. Overseas, Chugai Pharma USA and Chugai Pharma Europe are engaged in clinical development activities in the United States and Europe. Additional information is available on the Internet at http://www.chugai-pharm.co.jp.