Senolytics

JOHN said:
In your opinion do you think Unity Bio has a shot with their next trial on vision?

     I wouldn't put any money on it.  Essentially, the flawed approach of Unity Bio involves repurposing a highly toxic anti-cancer drug that they call UBX-0101 and have patented for senolytic applications.  UBX-0101 cannot be used as a general senolytic because of its toxicity.  To avoid whole-body toxic effects, they inject UBX-0101 into relatively isolated body systems like the knee capsule or the eye capsule.  The problem with this approach, in my opinion, is that the cleared senescent cells need to be replaced with healthy one, they are not clearing nearby senescence outside the capsule, and the SASP effects of these neighboring senescent cells are preventing replacement by stem cells.

    In my view, one needs to use a general non-toxic senolytic that clears all senescent cells.  Oisin Bio's DNA plasmid/liposome technique does this.  The recent Chinese paper describing a new synthetic small-molecule senolytic called SSK1 that targets the senescence-marker beta-galactosidase seems to promise to do the same.  However, the toxicity of SSK1 under all conditions has not been well established, it has not been tested on humans, and all senescent cells do not express beta-galactosidase.  Both such treatments should be followed up by providing a supply of pluripotent stem cells to replace the cleared senescent ones.