A Profile of UNITY Biotechnology

An accumulation of senescent cells is one of the causes of aging, and periodic removal of senescent cells is therefore one of the foundations for near future rejuvenation therapies. The first generation of these treatments will likely be available via medical tourism within the next couple of years, but we'll be waiting five years or more for comprehensive human data and passage through the regulatory systems of the US and Europe. For those who have been following events in the nascent senescent cell clearance industry, there won't be much that is new in this popular press article on UNITY Biotechnology, but it is nonetheless an interesting read:

In 2011, Jan van Deursen's team at the Mayo Clinic published research showing that when scientists regularly eliminate senescent cells from mice, the animals remain youthful longer; older mice who got similar treatment appeared to stop aging, based on measures of their mobility, muscle mass, and fat storage. When Nathaniel David saw the paper, he knew had to talk to the authors. Within 72 hours, he and Van Deursen were discussing forming a company. "This is my sixth company. You get kind of pattern recognition on things that feel 'druggable.'"

David was part of the team at Kythera Biopharmaceuticals, bought in 2015 by Allergan for $2.1 billion. Kythera's claim to fame was the development of Kybella, a drug for double chins that literally explodes fat cells. While the Food and Drug Administration considers double chins a reasonable therapeutic target for drug development, it doesn't feel the same way about aging. So even though Van Duersen's Mayo Clinic team showed this past February that clearing senescent cells from middle-aged mice led to a 20% increase in average lifespan versus control animals, UNITY has to focus its therapies on certain conditions. Anyway, David bristles at the idea that UNITY is an "anti-aging" company. The claim, he says, implies that biologists have already figured out what controls the fundamental ticking of the human aging clock. They haven't. Meanwhile, David expects UNITY to test its first drug, for osteoarthritis (OA) of the knee, in humans within 18 months.

Right now, patients with OA of the knee typically get cortisone injections into the joint every few months to treat the pain. Those shots appear to temporarily shut down senescent cells' ability to secrete proteins that cause inflammation, which essentially is the immune system turning on normal tissue, resulting in damage and stiffness. UNITY's drug will be delivered similarly through regularly scheduled injections, but would instead trigger the cells' deaths. Since the offending cells would be gone instead of temporarily muted, their injection could be given every year or two. If you had to pick one medical indication or element associated with aging to go after, says Matt Kaerberlein, an expert in the biology of aging at the University of Washington, "osteoarthritis is a great place to be. It's a specific indication, but it's a indication that could have a huge impact of quality of life for a lot of people."

There are concerns about side effects. For one, senescent cells also play a role in preventing cancer: cells can go into senescence to avoid become cancerous, acting as a sort of cancer emergency brake. David says the key is to make sure that UNITY's drugs don't "screw with the emergency brake." In other words, the company's therapies must avoid preventing cells from becoming senescent, and rather just eliminate them once they've gone down that path. Second, senescent cells play a role in healing wounds, and are often recruited to areas in the body where there's been trauma. Research done by Unity cofounder Judith Campisi has shown that in animals without senescent cells, wounds take longer to heal. A challenge facing Unity is figuring out dosing and treatment schedules to ensure that some senescent cells are available to restore tissues.

For David, the serial entrepreneur, the science behind UNITY is simply irresistible. And the excitement in his voice is audible when he talks about people aging in calendar years without deteriorating physically. While David doesn't believe that his company's therapies will radically increase lifespan, he does see an opportunity to profoundly extend "health span" - body part by body part. "Rather than dying at age 83, demented and catheterized in your bed, how'd you like to die at 107 on the tennis court while winning or be killed by a jealous lover at 112? That's in the realm of the possible with this biology."

Link: https://qz.com/878446/unity-biotechnology-cure-for-aging/


can you predict the impact of SCC on human lifespan?

Posted by: DV at January 9th, 2017 6:21 AM

@DV: No, but arguments can be made. I think that David overstates the likely outcome of senescent cell clearance alone, which is an interesting contrast to his unwillingness to talk about outright life extension as a goal.

The points to consider are that (a) while we know that extension of mouse longevity doesn't translate to the same extension in humans for attempts to slow aging by altering metabolism, this isn't the same class of approach at all, and there's nothing to really compare with yet, (b) there are a bunch of other types of damage that will kill you just as dead on much the same timeframe, even absent cellular senescence, but (c) the consequences of those forms of damage interact with cellular senescence and its consequences to make one another worse, so removing one may reduce the impact of all, while (d) we don't have any good handle on quantifying the scale of that interaction and won't until therapies exist, and (e) the full working suite of rejuvenation therapies that will radically extend life requires senescent cell clearance as a component part.

So the bottom line is who knows, more data needed. All the theory and animal studies point to this being much more beneficial for a range of age-related conditions and declines than any therapy presently available, and it is needed in the bigger picture for rejuvenation therapies in any case, so there are compelling reasons to move ahead even if you guesstimate the overall effect on life span from this one treatment applied in isolation to be small.

Posted by: Reason at January 9th, 2017 6:39 AM

We dont really know because nothing has directly tackled one of the Hallmarks of Aging yet like this. Inflammation both from senescent cells and "inflammaging" is a major driver of aging so the effects could significant. If anything it would probably help life expectancy even if it does not increase lifespan in humans beyond the 120ish limit.

Posted by: Steve Hill at January 9th, 2017 10:53 AM

I think SCC in combination with clearance of extracellular junk like amyloid and and arterial plaque, which are on the near horizon, could lead to pretty significant gains in life extension. Especially if combined with stem cell replacement of youthful cells, kind of like an oil change.

Posted by: Link at January 9th, 2017 4:30 PM
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