Genflow Biosciences is working on a gene therapy to deliver a variant SIRT6, a protein involved in DNA repair, and thus touches on many aspects of aging. Upregulation of SIRT6 modestly extends life in mice, accompanied by what looks like a better maintenance of mitochondrial function into old age. Versions of SIRT6 found in short-lived mammalian species appear to produce a worse efficiency of DNA repair than the version found in long-lived mammalian species.
The Genflow principals intend to deliver a SIRT6 gene therapy as a compensatory approach to DNA repair deficiency conditions, such as Werner syndrome, that have the appearance of accelerated aging. This is hoped to be a stepping stone to later attempts to treat aging. It remains an interesting question as to what adjustments to DNA repair efficiency can do for long term health in long-lived mammalian species such as our own. Is this yet another case, like stress response upregulation, in which modest effect sizes in mice turn into negligible effect sizes in humans? The only practical way to find out is to try.
Key to Genflow's approach is a collaboration with Vera Gorbunova - a member of the company's scientific advisory board, and well known for her research into SIRT6. "In 2019, Vera published a paper that showed, in rodents, you could have a very good correlation between lifespan and the quality of SIRT6. She found she could increase or decrease the lifespan of rodents based on the variant of SIRT6 that she was providing." This led researchers wonder whether it was possible to find a "better" SIRT6 than the one that already exists in humans. "We discovered that it was possible, thanks to the discovery of a variant of SIRT6 only found in centenarians. So we decided to create a company that will deliver this SIRT6 variant in order to prevent the accelerated aging process."
"Ten years ago, gene therapy was a bad word associated with high cost and high toxicity - a dangerous last resort therapy. Now you see progress in AAVs every week. Today we have AAVs that are almost invisible to the immune system, they are non-integrating, their cost has decreased substantially, and there are now more than 40 companies developing clinical trials with AAVs. So, it's now possible to have an ethical, patient friendly and cost-effective intervention at the genetic level."
While progeria, Werner's syndrome, and other indications are in the company's pipeline for eventual human trials, Genflow is really only thinking about targeting aging. "One of the differences between us and other longevity companies is that we are fully dedicating to longevity. Yes, we will have a trial in Werner's syndrome, but we consider that a door opener to having a true aging indication. At one point, we know that the regulatory agencies will change their mindset on this - we see an evolution - and we want to be positioned to be to take advantage of that."