Oisin Biotechnologies Launches New Website

Oisin Biotechnologies is a senescent cell clearance company founded by long-standing members of our community, seed funded by the Methuselah Foundation and SENS Research Foundation, and supported by the investment of a number of folk in the audience here. Targeted removal of senescent cells is a form of narrowly focused rejuvenation, shown to turn back numerous measures of aging in animal studies, and the Oisin team has made great strides in proving out their programmable gene therapy approach. This sort of commercialization project is exact what our community has been working towards all these years, and the faster that implementations reach the clinic, the better off we all are.

Oisin Biotechnologies' ground-breaking research and technology is demonstrating that the solution to mitigating the effects of age-related diseases is to address the damage created by the aging process itself. Our first target is senescent cells. When cells detect that they have been irretrievably damaged, they enter a non-dividing condition known as cell-cycle arrest, or senescence. It's believed this occurs to prevent cells from going rogue and turning cancerous. Ideally, they should die by the process known as apoptosis, but as we age, more and more frequently they don't. They become zombie cells - unable to kill themselves or resume normal function.

Senescent cells secrete molecules that cause inflammation in an effort to attract immune cells that would usually clear them. But for reasons that are not fully known, as we age, persistently senescent cells accumulate, leading to a vast number of age-related diseases. Oisin is developing a highly precise, patent-pending, DNA-targeted intervention to clear these cells. As a recent study has shown, clearing senescent cells both reduces negative effects of aging pathologies and also extends median lifespan and survival.

There are two major challenges to clearing senescent cells using our approach. First is to design and create the DNA construct that recognizes that a cell has become senescent, and then destroys it. Second is to safely and efficiently deliver this construct into cells throughout the body. Both goals have been achieved in our pioneering proof of concept experiments in 2016. We've first demonstrated the ability to transduce cells both in vitro (cell culture) and in vivo (in aged mice). Then we showed that p16 positive senescent cells can be killed on demand in both in vitro and in vivo environments. Now we are embarked on experiments that will show improvements in both healthspan and lifespan in model organisms from mice to primates. And then, everything changes.

Our proprietary technology gives persistently senescent cells a helping hand to "do the right thing." By providing an exogenous apoptotic gene, which is only transiently expressed in cells that already have the p16 gene active, we can precisely induce the senescent cell to commit suicide. Oisin has shown as much as an 80% reduction in senescent cells in cell culture and significant reductions of senescent cell burden in naturally aged mice. SENSOlytics is an Oisin proprietary platform technology that enables precise targeting of a senescent cell based on the DNA expression of the cell, not on surface markers or other characteristics that might be shared with normal, undamaged cells.

Link: https://www.oisinbio.com/

Comments

'And then, everything changes.'

This is quite exciting.

I wonder, will we only see median (healthspan) improvements from senescent cell clearance? Results in mice would suggest so. But given that so many different types of cell damage end up with senescence, might we hope for more from a truly efficacious clearance?

Posted by: Mark at June 27th, 2017 8:41 AM

"SENSOLYTICS" ! They coined it.

Posted by: Norse at June 27th, 2017 8:45 AM

Good to see that they are being bold. Would love to see some before/after pictures of the mouse models.

The more sensory input we can give, the better. Seeing is believing.

Posted by: mborbely11 at June 27th, 2017 9:17 AM

@mborbely11 - The animals were sacrificed almost immediately; we've eschewed lifespan studies to date due to cost. Our view is that the lifespan and healthspan data accumulated by others in the academic sector already confirm the benefits of ablating senescent cells, so we don't have to spend effort repeating that work. We want to spend our resources killing those cells as efficiently as possible, and getting at least one indication to the clinic as fast as we can.

Posted by: Gary at June 27th, 2017 1:46 PM

I don't want to be a wet blanket, but this treatment could still run into multiple problems once they start testing it in humans. Like the LNP delivered siRNA drugs, the LNPs of Oisin will tend to accumulate in the liver, leading to possible toxic side effects:

http://www.fiercebiotech.com/biotech/arrowhead-snaps-after-trial-hold-as-it-targets-major-layoffs-ditches-programs

"In a call to investors last night, Dr. Christopher Anzalone, president and CEO, said: "While a path forward has been taking shape [on ARC-520], it is becoming increasingly clear that the nonclinical studies required to test our hypotheses would be complicated, time-consuming, and expensive.

"Why is that? We still do not know why some of the primates died at the highest dose, which, as we have said previously, is higher than human doses. Our hypothesis is that they were caused by dose related drug-induced toxicity exacerbated by extensive study-related handling procedures and infusion reactions for which the animals are not pretreated, unlike patients and volunteers in our clinical studies who receive an oral antihistamine prior to treatment."

This may not happen with Oisin's lipid nanoparticle, or Oisin's LNP may be different from those used by Arrowhead and Alnylam in some way?

Posted by: Jim at June 27th, 2017 3:36 PM

@ Jim - yes, that's what we use. Tox studies done to date (as well as our treatments in vivo) demonstrate no signs of liver toxicity, due to the particular type of LNPs employed. I don't want to go into too much detail on this point, at this time, however.

Posted by: Gary at June 27th, 2017 4:57 PM

Thanks for answering Gary! So nice to have the actual people doing the experiments so engaged with the community!

Quick question if you have time.. these experiments measuring healthspan/lifespan, what kind of time frame are you hoping to have all the data gathered?

Posted by: mborbely at June 27th, 2017 6:03 PM

@mborbely1 - Even with short-lived mice and starting with aged animals, lifespan studies could take the better part of 12-24 months. Better to run trials in humans looking at specific indications, and measure increases in function, which should translate into healthspan and lifespan gains based on analogy to already-performed animal experiments.

Posted by: Gary at June 27th, 2017 6:17 PM

For some 50 yr, I've noticed that most think that one unit of clock time is and must be one unit of aging time. I call this the one-to-one fallacy. The whole point is to make one unit of aging time take far, far longer than one unit of clock time.

Posted by: Tatiana Covington at June 28th, 2017 10:54 PM

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