Fight Aging!

The longevity industry is presently still quite young, a hundred and something companies that are largely still at the preclinical stage of development, most founded in the last couple of years. Even if we want to be broadly generous as to which companies and projects are to be included in our definition of the industry, no newly developed therapies to treat the mechanisms of aging have yet been approved by the FDA, although a few have made it to phase 3 clinical trials. This is just a matter of time, however; it can take a decade of hard work to go from an idea to an approved therapy, and very few longevity industry companies are even half that age.

Of perhaps more immediate interest are existing approved drugs that appear to have a meaningful effect on mechanisms of aging. The most important of these are widely used chemotherapeutics that have been found to selectively kill senescent cells, and thereby produce rejuvenation in mice. No-one noticed this potential for intervention in the aging process while such drugs were being developed in animal models of cancer and used in cancer patients, for all the obvious reasons. The dosing was quite different, the lifespans of the animals and patients largely quite short, and the disruptions of cancer and high dose chemotherapy masked the benefits that can be obtained via a different approach to usage.

Back to the new therapies under development and the rapidly growing longevity industry, there is more than enough work taking place at present for a community of speculators and spectators to emerge, of various degrees of organization, professionalism, and commercial inclinations. I'll point out one of the more market-focused examples today, with a couple of posts that tour the handful of longevity industry clinical trials underway or recently conducted. Not all are targeting aging, such as the work of Gensight on allotopic expression of mitochondrial genes to treat inherited mitochondrial disease, and these are only relevant because they exercise approaches that can later be turned to address aging.

#015: A Review of Every Single Longevity Therapy in Clinical Trial Today. (PART 1)

Currently there are 28+ anti-aging therapies in human clinical trials spanning a variety of strategies, targets, indications, companies, and modalities. The trials are conducted by companies - private and public - but also universities and non-profit groups. There are also perhaps 100 more pre-clinical companies working on aging in addition to this effort. If any one of the therapies in the first volley on the problem of aging achieve success - even if modest - it could trigger investor hype rivaling the biggest bubbles in history. The zero to one moment in human life extension will change everything.

With the exception of maybe Nir Barzilai's TAME metformin trial (not yet registered), none of the anti-aging therapies currently being tried directly use aging as their clinical endpoint. Most trials instead measure a therapy's efficacy with respect to a specific age-related disease rather than aging itself. Or sometimes the indication is a disease that can be treated with a tool developed from an aging perspective. This is because: (1) The FDA does not recognize aging as an indication (yet). (2) It is expensive to run trials that measure lifespan in humans. (3) We don't have have robust surrogate biomarkers for aging (yet). (4) It is easier to demonstrate clinical significance in an age-related disease than aging itself.

#016: Every Single Longevity Therapy in Clinical Trial Today (PART 2)

Aging is a malleable biological process. Scientists have been precisely turning the knobs of aging in model organisms since the 1990s. Presently we have reached an inflection point: Therapies developed in the context of longevity science are being tested in human patients today.

LYG-LIV0001 - LyGenesis

Perhaps one of the more ambitious clinical trials. LyGenesis is a Juvenescence-backed startup spun out of research at the University of Pittsburgh. The company is attempting to regrow livers by injecting allogenic liver cells into patient lymph nodes. The lymph nodes act as bioreactors and slowly regrow into functional livers - at least in the pre-clinical experiments done on pigs. Their Phase 2 trial includes patients with end-stage liver disease. If successful the company plans to also use the same strategy to regrow the thymus (reversing immunosenescence) and also pancreatic islet cells (reversing diabetes).

SkQ1 - Mitotech

Mitotech is an anti-aging company that develops therapies that protect the mitochondria from reactive oxygen species (ROS). SkQ1 is an anti-oxidant that can easily penetrate the mitochondrial membrane where it can inhibit ROS. In particular, SkQ1 protects cardiolipin, an important protein found in the inner mitochondrial membrane. Dry eye might not sound like a very sexy anti-aging therapy. But this trial is just one small step in the journey of treating mitochondrial diseases, many of which are age-related.

Nicotinamide riboside - ChromaDex

NAD+ levels decrease with age so the hypothesis is that boosting NAD+ levels can have potential anti-aging benefits. There are several chemical precursors to NAD+ but the two most popular are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). ChromaDex is the patent holder of NR and sponsors a number of clinical trials to support the case for its potential anti-aging properties. This time they are measuring hospitalization duration for patients with tissue damage. Given the small size of the study (84 participants) and probable heterogeneity in the illnesses, I have a hard time seeing how anything definitive will be elucidated. This is just one trial of many exploring the benefits of NAD+ precursors / booster. These NAD+ precursor compounds are generally considered safe so I'm excited to see what can benefits can be demonstrated in trials.