It Looks Like UNITY Biotechnology is Taking the Drug Development Path to Senescent Cell Clearance

UNITY Biotechnology and Oisin Biotechnologies are both early stage startups working on commercial development of therapies capable of clearance of senescent cells. Since accumulation of senescent cells is one of the root causes of aging and age-related disease, periodic removal of these cells is a narrowly focused form of rejuvenation. There are a number of other forms of damage and disarray that contribute to degenerative aging, and all will have to be fixed if aging is to be controlled by medicine, but an individual with fewer senescent cells is absolutely better off than one with more senescent cells regardless of the state of other forms of damage. Earlier this year researchers associated with UNITY Biotechnology published the results of the first life span study in normal mice engineered to destroy their own senescent cells, showing a 25% extension of median life span.

While the Oisin Biotechnologies principals have been pretty open on the topic of how their approach to senescent cell clearance works - it is a form of sophisticated gene therapy - the path chosen by UNITY Biotechnology remains less clear. In part this is because the public research based on gene therapy in mice that led to the life span study noted above is not something that could easily be adapted for use in human trials: it could be done, but almost every other option on the table would be both substantially easier to accomplish and more palatable to regulators. There is a trail of patents for other research leading in to the merger of groups that formed the company, but they cover a fairly wide selection of possible methodologies, including the use of immunotherapies and engineered viruses.

Gene therapies, immunotherapies, and more esoteric modern medical technologies are not the only possible approach to senescent cell clearance, however. In the past couple of years research groups have produced classes of drug - now called senolytic compounds - that can selectively drive senescent cells to self-destruct via the process of apoptosis. The combination of dasatinib and quercetin, for example, removes enough senescent cells in enough different tissues to produce meaningful benefits in mice. It isn't unreasonable to think that this type of result can be improved upon to the point at which it is a competitive option. Judging from recent news, it seems that UNITY Biotechnology will take the apoptosis-inducing drug development path, and, interestingly, is also setting up from the outset to deploy therapies outside the US in less heavily regulated regions:

Ascentage Pharma and UNITY Biotechnology Announce Collaboration for the Development of Senolytic Healthspan Therapies

China-based Ascentage - which is currently working on apoptosis-targeted cancer treatments - will work with UNITY Biotechnology to develop senolytic treatments for age-related diseases in an attempt to roll the back years for seniors. UNITY said it has also demonstrated in animal models that clearing senescent cells reverses or prevents many age-related pathologies, including: osteoarthritis, atherosclerosis, glaucoma, and kidney disease. "At UNITY, we have demonstrated that senescence is a key mechanism in aging and age-related disease. We have evaluated a wide panel of drug candidates that clear senescent cells, and Ascentage's compounds are some of the best we've seen. Access to their compound library through this collaboration will significantly accelerate our efforts to develop drugs to improve healthspan by halting or reversing several age-related diseases."

The biotech chose Ascentage as its partner in this anti-aging field "not only because of its cutting-edge technology, but also because this partnership will allow us to reach a global market." As part of the deal, the companies will also form a joint venture for the development and commercialization of senolytic drugs in China. Though specific terms are undisclosed, Ascentage has said it will acquire an equity interest in UNITY, and in return, the company will make an investment in Ascentage. Robert Nelsen, the co-founder and managing director of ARCH Venture Partners and a UNITY board member, will join the Ascentage board as an observer.

Ascentage Chairman and CEO Dr. Dajun Yang added, "We are one of the leading biopharmaceutical companies with clinical stage compounds targeting key proteins that control programmed cell death pathways. We will continue our efforts to advance clinical stage compounds for targeted anti-cancer therapy and are very pleased to work with UNITY for several unmet medical indications outside of the oncology space, with each aging-related disease potentially representing a multi-billion-dollar market."

Comments

I personally doubt that this approach will work in humans. My thinking is that we are pushing the boundaries of our age limits as it is, and we are limited by poor DNA replication/repair mechanisms. This, I believe, is demonstrated by the Alzheimer's/Cancer tradeoff, which shows that People with Alzheimer's have lower cancer rates and vice-versa. People with cancer have higher repair rates, through lower controls on replication, Alzheimer's sufferer's have tighter controls on replication and thereby reduced repair rates.

Senescent clearance would be a very low-hanging fruit biologically speaking. There are already biological mechanisms in place to do this. UNLESS research shows that super-centenarians use this mechanism, then I doubt it will work.

Posted by: Benjamin Wade at April 27th, 2016 4:40 PM

@Benjamin quite the contrary, the data that is coming in for Senolytics (there have been many papers in the last year in particular) suggest Senolytics would be a very good choice. You say there are already biological mechanisms in place, yes there are, however systems such as the immune system which cull senescent cells decline with age and these "death resistant" cells accumulate in greater amounts driving chronic inflammation and contribute to signalling decline.

Studies removing them have shown improvement of various health issues such as cardiovascular, lungs, skin and more. It is very likely a large determinant of your lifespan is inflammation and senescent cell burden. A newcastle University Study in fact showed than chronic inflammation was a significant determinant of living to extreme old age with slow telomere loss helping to get to around 90 or so.

Posted by: Steve Hill at April 28th, 2016 10:54 AM

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