FightAging!
7-1-18

https://www.fightaging.org/archives/...lytic-therapy/

The honor of running the first trial of a senolytic drug, albeit inadvertently, goes to one of the groups testing dasatinib or navitoclax back when those pharmaceuticals were first evaluated for cancer therapies. At that time nobody knew that these drugs could selectively destroy senescent cells, and were thereby far more valuable as a starting point for rejuvenation therapies than as cancer treatments. The first intentional human trial was started last year by Betterhumans, a non-profit organization. Now Unity Biotechnology has recently announced that their first human trial is underway, testing the ability of their initial candidate senolytic to treat osteoarthritis. You may recall that the evidence in animal models for the accumulation of senescent cells to be a primary cause of osteoarthritis is fairly compelling. We can hope that this holds up in humans; results will likely start to appear in a preliminary form next year.

UNITY Biotechnology, Inc., a biotechnology company developing therapeutics to extend healthspan by slowing, halting, or reversing diseases of aging, today announced the treatment of the first patient in the Phase 1 clinical trial evaluating UBX0101 in moderate to severe osteoarthritis of the knee. "For many people, we believe that osteoarthritis is the main reason why it hurts to get old. By designing a treatment to selectively eliminate senescent cells in the joints of patients diagnosed with painful osteoarthritis, our goal is to alter the otherwise disabling course of this disease. This is an important milestone for UNITY. This is the first time we have treated a patient with a drug to eliminate senescent cells. While this study is designed to establish safety, we are also looking for the earliest signals of reducing senescent cell burden in this disease of aging."

The Phase 1 clinical trial of UBX0101 is a randomized, double-blind, placebo-controlled, single ascending dose study that will evaluate safety, tolerability, and pharmacokinetics of a single intra-articular injection of UBX0101 in patients diagnosed with moderate to severe osteoarthritis of the knee. Patients will be randomly assigned to receive UBX0101 or placebo in 3:1 randomization by dose level cohort.

Cellular senescence is a natural biological state in which a cell permanently halts division. Senescent cells accumulate with age and secrete as many as 100 different biologically active proteins, including pro-inflammatory factors, proteases, pro-fibrotic factors, and growth factors that disturb the tissue microenvironment. This collection of secreted proteins is referred to as the Senescence Associated Secretory Phenotype, or SASP. In addition to its effects on tissue function, the SASP contains factors that induce senescence in neighboring cells, setting off a cascade of events that culminates in the formation of the functionally aged and/or diseased tissue that appears to underlie a variety of age-associated diseases. UNITY believes that the elimination of senescent cells will remove SASP factors - addressing a root cause of diseases of aging. Senolytic medicines, or treatments designed to selectively remove senescent cells, target the SASP at its source, and may have a more durable impact on disease than current therapies.