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Nature Medicine Study Describes a Novel Senolytic Molecule that Slows the Progression of Osteoarthritis

SAN FRANCISCO, April 24, 2017 /PRNewswire/ -- UNITY Biotechnology, Inc. announced today the publication of new research in the journal Nature Medicine demonstrating that the selective elimination of senescent cells with a drug may delay, prevent, or even reverse the progression of osteoarthritis (OA), the age-associated inflammatory condition causing chronic joint pain in 80% of people over 65. Researchers found that senescent cells accumulate in the knees of mice, and that the selective elimination of these senescent cells using UBX0101 – UNITY's first-in-class senolytic molecule – slowed the progression of disease, reduced pain, and induced cartilage production in human knee tissue grown in culture.

The study was conducted by researchers from UNITY Biotechnology, Johns Hopkins University, Buck Institute for Aging Research, Lawrence Berkeley National Laboratory, Mayo Clinic College of Medicine, Ulsan National Institute of Science and Technology, and the European Research Institute for the Biology of Ageing.

"For decades, OA has been thought of as a chronic inflammatory disease," said Nathaniel David, Ph.D., president of UNITY Biotechnology and an author of the study. "The big mystery in OA was where the inflammatory molecules were coming from. Our new work answers this question, at least in part. It appears that the inflammatory factors that drive OA are made by senescent cells. You eliminate senescent cells, and you stop OA."

Mark Genovese, M.D., professor of medicine, division of immunology and rheumatology at Stanford University School of Medicine, added: "This is a unique approach to the treatment of osteoarthritis and if it can be translated into a therapeutic approach for human OA, it could result in a major change in the way we treat the disease."

Key findings:
Senescent cells contribute to progression of OA in mice
Osteoarthritis was induced in both young and old mice by using a standard ACL transection (ACLT) model. The resulting mechanical instability of the joint drives the accumulation of senescent cells in the articular cartilage and synovial membranes of the knees. The senescent cells appear within weeks of ACL transection and symptoms of OA are evident at 30 days.    

A similar accumulation of senescent cells occurs naturally over time as mice age, resulting in cartilage destruction without any surgical intervention. In mice, elimination of senescent cells from 12 months onwards maintains youthful cartilage, even in animals as old as 28 months (equivalent to approximately 80 years old for people).

UBX0101 reduces disease impact and creates a pro-chondrogenic environment in mice
Following clearance of senescent cells with UBX0101 in the ACLT model, both OA-related pain and cartilage erosion were reduced, and cartilage began to regenerate.   

Results were validated in a human knee tissue grown outside the body
In cartilage grown from human knees with advanced OA, UBX0101 selectively eliminated senescent cells, increased proliferation of healthy chondrocytes, and induced new cartilage growth.

The full article, titled "Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment," is available through the Nature Medicine website (doi: 10.1038/nm.4324). A list of recent published studies by UNITY researchers, collaborators, and cofounders is available on the UNITY website.

About Osteoarthritis
Osteoarthritis (OA) is a degenerative joint disease characterized by the gradual loss of joint cartilage, distorted bone growth, joint inflammation, and joint pain. Eighty percent of individuals over 65 years of age have some form of OA as assessed by X-ray radiographic analysis, suggesting that this disease impacts a majority humans by the time they are in the latter third of life. Presently, there are approximately 27 million people affected in the United States alone, with an anticipated increase in the prevalence to nearly 45 million by 2030. Standard of care begins with NSAIDS (non-steroidal anti-inflammatory drugs), injection of corticosteroids, and ultimately mechanical replacement of the affected joint. The root cause of this debilitating chronic illness has not been elucidated, and no disease modifying therapies yet exist.

About Cellular Senescence and Senolytic Medicines
Healthy cells that experience stress can enter a state known as cellular senescence. In this state, cells stop dividing and profoundly alter their metabolism, appearance, and interactions with their environment. Cellular senescence is a critical anti-cancer system, as it stops potentially damaged cells from growing out of control. However, senescent cells can accumulate in the body as we age, secreting growth factors, proteases, and inflammatory factors that disrupt normal tissue function. This may be a contributor to the chronic inflammation observed in many age-related diseases.

Based on recent discoveries in the rapidly advancing field of cellular senescence, UNITY is developing a new class of therapies for diseases of aging called senolytic medicines. These medicines are designed to selectively eliminate senescent cells linked to diseases of aging, such as osteoarthritis, glaucoma, and atherosclerosis. Recent studies published in ScienceNature, and Nature Medicine demonstrate how the selective elimination of senescent cells may prevent, delay, or even reverse diseases of aging. UNITY expects to initiate its first clinical study in OA of the knee in 2018.

About UNITY Biotechnology
UNITY Biotechnology is developing therapeutics that increase healthspan by preventing, halting or reversing diseases of aging. UNITY's initial focus is on creating senolytic medicines to selectively eliminate senescent cells and thereby treat age-related afflictions such as osteoarthritis, atherosclerosis, eye diseases, and kidney disease. Backed by a group of visionary investors, UNITY's world-class management team has experience building companies and developing medicines together: the team has collectively moved more than 90 therapeutic candidates into human clinical trials and developed 13 FDA-approved medicines. UNITY's mission is to build a future in which it doesn't hurt to be old — a future in which people stay healthy and mobile long into old age. More information is available at www.unitybiotechnology.com.


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