Send in the senolytics
Despite early failures in the clinic, the idea of anti-aging therapies that purge the body of dying cells is gaining traction with a raft of startups now focused on senescence.
Unity Biotechnology was one of the darlings of the nascent anti-aging biotech sector. With big-name investors, such as Jeff Bezos and Peter Thiel, an impressive lineup of academic founders and a market valuation that once reached $700 million, the company was, in effect, the industry’s standard-bearer for the therapeutic idea of destroying senescent cells to blunt the ravages of aging.
In August, that idea took a hit when Unity announced that its lead drug candidate had failed to beat a placebo in reducing joint pain and stiffness, according to interim results from a trial of patients with osteoarthritis of the knee. The company’s stock plunged more than 60% on the news, nearly one-third of Unity staff were laid off, and its experimental drug UBX0101 — the first novel ‘senolytic’ agent ever to enter clinical testing — was swiftly abandoned.
That setback threw a pall over the entire senolytic field. A research note from Citi analyst Yigal Nochomovitz cited “substantially greater risk to the senolytic hypothesis.” However, other experts were more sanguine about a class effect, highlighting issues with trial design, study population and UBX0101 itself — a small-molecule inhibitor of MDM2 (murine double minute 2) designed to boost the activity of the proapoptotic p53 protein — as possible explanations for study failure.
In the meantime, more than two dozen other startups continue to pursue approaches to target senescent cells — strategies that range from cell destruction and containment to senescence prevention and even reversal.
Continue reading at Nature Biotechnology.
