Senolytic will be tested on people
Clinical trials of the first anti-aging therapy
Nicola Bagalà and Steve Hill, LEAF
The First Rejuvenation Therapy Reaches Human Trials
Translation: Ariel VA Feinerman, Habr
We are pleased to announce that UNITY Biotechnology has started clinical trials on humans of the first true anti-aging therapy that directly targets one of the causes of aging: senescent cells.
Peaceful revolution
In our collective imagination, revolutions begin with an explosion; however, most often, real technological revolutions begin quietly and without the knowledge of most people. This is largely what happens with therapy, which aims to prevent or reverse age-related diseases by directly targeting the causes of aging.
The very first human trial of senolytic drugs was announced back in June, and most of the world paid little attention to it, and what its success could represent for the future of medicine. We're talking about a statement UNITY Biotechnology about the beginning of trials of its senolytic drug UBX0101 in patients suffering from osteoarthritis.
Senolytic educational program
Senolytics are a class of drugs that can potentially affect senescent cells, which are one of the causes of aging. Simply put, a cell becomes senescent when it loses the ability to divide. This happens as a response to DNA damage, and therefore it is a kind of protection in order to prevent the reproduction of cells containing mutations, for example, such as cancer. This response may be caused by telomere depletion, since the cell performs the maximum number of divisions it is capable of, or other external stresses, such as oxidative stress.
Cellular aging helps prevent cancer and is important in wound healing; however, the accumulation of senescent cells over time appears to be harmful. Senescent cells secrete a cocktail of chemicals known as the aging-related secretory phenotype (SASP), which is associated with a number of age-related diseases; SASP promotes tissue inflammation and causes aging in neighboring healthy cells, initiating a chain reaction.
While senescent cells are usually destroyed by the immune system, an increasing number are avoiding destruction due to immune aging – an age-related decline in the ability of the immune system to do its job. This, in turn, leads to the accumulation of senescent cells and an increase in chronic inflammation.
For several years, it has been suggested that selective elimination of senescent cells can reduce, potentially stop and reverse some age-related pathologies; several bioengineering companies have developed various types of senolytics targeting senescent cells, leaving healthy cells intact. The results on mice of different ages were very good, but the only way to find out whether the senolytic will be useful to humans is to run a clinical trial on humans.
UNITY Biotechnology and UBX0101 Testing
UNITY Biotechnology was founded in 2011 by Jan van Duersen, Judith Campisi, Nathaniel David and Daohong Zhou. UNITY focuses on the destruction of senescent cells, but the company is also working on mitochondrial dysfunction and the loss of circulating juvenile factors. Her plans include several drugs that are currently in the optimization phase, and UBX0101 has just entered phase 1 of a randomized, double-blind, placebo-controlled, FDA-approved clinical trial.
UBX0101 is currently being tested for safety in patients suffering from mild and severe osteoarthritis, an age-related pathology affecting joints and causing cartilage and bone destruction. This pathology can cause joint swelling, decreased mobility, joint pain and stiffness, affecting daily life. Cellular aging is associated with osteoarthritis, and affects different joints, but UNITY's current research focuses on knee osteoarthritis. Although this test is primarily intended to assess the safety and tolerability of a single injection, the effectiveness will also be monitored.
What's next?
It's too early to say how well senolytics will work on humans, but regardless, the process can be considered an important milestone on the way to a world free of aging. Despite the fact that this study focuses on a specific pathology, UNITY's approach is aimed at the primary cause of aging, at reversing the disease or at least slowing it down; currently osteoarthritis is treated – like most age–related pathologies - only symptomatically.
If the trial is successful, it will attract more resources for such research in order to further improve the approach and possibly expand it to the treatment of other pathologies; other companies may follow UNITY's example and join the race to improve the technology that has already shown its effectiveness; more generally, a successful senolytic trial will provide proof of concept, that human aging is amenable to medical intervention not only in theory, but also in practice. This may prove to be a fatal blow to the pro-aging trance, which leads many people to believe that it is not necessary to interfere with aging.
UNITY also has a second candidate for senolytics, UBX1967, an inhibitor of specific members of the BCL-2 family of regulatory apoptosis proteins, which is scheduled for phase 1 clinical trials in the treatment of eye diseases in the second half of 2019.
Conclusion
This is the first true anti-aging therapy in human clinical trials based on a repair approach to aging, developed back in 2004 by Aubrey de Gray of SENS. The removal of these problematic cells has long been proposed as a way to combat age-related pathologies and, we have reached the point where more than ten years of research are finally ready to be tested.
If the trial fails, it will still provide us with invaluable information, deepen our understanding of aging, and allow us to try again. In any case, it will be a win-win option. We are happy to update our Rejuvenation Map to include UNITY, and we wish them success!
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