Another senolytic drug candidate has entered development at Unity Biotechnologies. The purpose of senolytics is to clear the body of harmful senescent cells, which accumulate with age and encourage age-related diseases to develop.
A new treatment for age-related diseases of the eye
Recently, UNITY Biotechnologies announced the selection of a new lead drug, UBX1967, with the goal of treating a range of age-related diseases of the eye. This is the second drug in the pipeline of this $677 million company. This drug is unique in the world of eye treatment; it targets and destroys senescent cells, making it a senolytic that targets one of the root causes of aging to treat disease.
This means that the drug may have a wide range of effectiveness among age-related diseases, and, if it’s effective, it could have the ability to also treat age-related diseases not involving the eyes, given the wide range of diseases and disabilities thought to be caused in part by cellular senescence [1-3].
Where are we now?
It’s important to put this development into perspective, though. This therapy is at an early stage, even compared to UNITY’s competition. The drug will now go through testing to qualify for an “Investigational New Drug” (IND) classification in the second half of 2019, which, according to the FDA website, allows shipment of the drug across state lines, making it the first step towards starting human trials.
In order to qualify for IND classification, the drug will have to go through a series of animal trials, testing toxicity. If the therapy is deemed safe enough for human testing, the IND application will then be sent to the FDA. 30 days will then pass before human trials can begin. At that point, the therapy must pass three phases before it may be sold. This is a long path, spanning years, but the first steps have already been taken.
It is also important to temper our expectations. A small percentage of drugs that begin clinical trials are accepted for use, with most either being toxic or ineffective [4]; still, it could be argued that UNITY’s strategy of targeting one of the hallmarks of aging may give UBX1967 a better chance of success.
How does it work?
UBX1967 effectively ‘turns off’ certain signaling proteins in the BCL-2 family. These proteins encourage cells to not activate programmed cell suicide, otherwise known as apoptosis. With these proteins disabled, certain types of senescent cells that rely on these particular proteins for survival are destroyed.
The goal is to reduce the impact of these senescent cells on their surrounding organs, preventing them from releasing inflammatory chemicals, which cause diseases and other harmful effects.
Summary
UBX1967 is a new senolytic drug developed by UNITY Biotechnologies, which aims to treat a number of age-related diseases of the eye. As it specifically targets a hallmark of aging, it may turn out to also be useful in the treatment of some other age-related diseases.
Before human trials may begin, it must go through animal trials in order to attain an IND classification. While this therapy is promising, we must temper our expectations with the knowledge that a vast majority of therapies that reach this stage fail their trials and are abandoned.
Literature
[1] Joshua N Farr, Ming Xu, Megan M Weivoda, David G Monroe, Daniel G Fraser, Jennifer L Onken, Brittany A Negley, Jad G Sfeir, Mikolaj B Ogrodnik, Christine M Hachfeld, Nathan K LeBrasseur, Matthew T Drake, Robert J Pignolo, Tamar Pirtskhalava, Tamara Tchkonia, Merry Jo Oursler, James L Kirkland & Sundeep Khosla (2017). Targeting cellular senescence prevents age-related bone loss in mice. Nature Medicine (2017) doi:10.1038/nm.4385.
[2] Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018). Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature, 562(7728), 578.
[3] Dalle, S., Rossmeislova, L., & Koppo, K. (2017). The role of inflammation in age-related sarcopenia. Frontiers in physiology, 8, 1045.
[4] Chi Heem Wong Kien Wei Siah Andrew W Lo (2018). Estimation of clinical trial success rates and related parameters. Biostatistics, kxx069, https://doi.org/10.1093/biostatistics/kxx069
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