In the first part of this blog (link) I summarised some of the clinical trials currently investigating therapies aiming to slow down the biological aging process. Keep in mind that none of these therapies directly use aging as their clinical endpoint. In fact, most clinical trials measure a therapy’s efficacy with respect to a specific age-related disease —since it is expensive to run trials that measure lifespan in humans, and as there’s no consensus biomarker set for biological aging and FDA does not recognise this most complex process as an indication.
Today, I will continue the overview of other longevity clinical trials summarised here: Every Single Longevity Therapy in Clinical Trial Today by Nathan Cheng.
LYG-LIV0001: LyGenesis—a startup spun out of research at the University of Pittsburgh — is attempting to regrow livers by injecting allogenic liver cells into patients’ 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 (Data 2023 link) includes patients with end-stage liver disease, trying to restore liver function (ectopic liver regeneration). If this proves to be successful the company plans to use the same strategy to regrow the thymus (reversing immunosenescence) and also pancreatic islet cells (reversing diabetes).
BIO101 – BioPhytis is a French company that is attempting to reverse age-related loss of muscle mass. Their approach uses small molecule drugs that are similar to the chemicals plants produce in response to environmental stress. The hypothesis, coined by David Sinclair as “xenohormesis”, is that the signalling molecules in the stressed plants (e.g. polyphenols) stimulate biological resilience in the animals that ingest them.
In particular, BIO101 phase 1 trial (Data December 2020, link) is trying to target the Mas receptor in muscles to stimulate the P13K/AKT/mTOR pathway and grow muscle. This is a little paradoxical as many longevity drugs (like rapamycin) attempt to inhibit mTORC1. BIO101 also activates the AMPK pathway that regulates metabolism and autophagy, which is similar to how metformin is believed to extend lifespan.
Rapamycin – PEARL Trial: AgelessRx, a direct to consumer longevity telehealth startup is running “PEARL” phase 4 trial (data December 2023) to test rapamycin on 200 older patients. Rapamycin, initially used as an immunosuppressant for organ transplant recipients, is one of the most studied life extending drugs known to reproducibly extend the lifespan of female mice by approximately 15%. During the study they will measure changes in visceral fat, bone density and various blood biomarkers.
CD34+ cells enriched with MNV-BLD: Minovia Therapeutics is trying to solve the problem of mitochondrial mutations in order to treat Pearson Syndrome — an ultra rare and fatal mitochondrial disease. By doing so, they are trying to address one of the 7 major “Strategies for Engineered Negligible Senescence” (SENS) regenerative medical therapies of aging identified by gerontologist Aubrey de Grey, also an AgeCurve adviser.
You can read more about Aubrey De Grey joining AgeCurve‘s Advisory Board in our previous blog (link).
Minovia’s phase 1/2 trial (data June 2021, link) involves extracting stem cells from the patient (CD34+ hematopoetic progenitor cells), infusing them with healthy mitochondria from the mother and injecting the cells back into the patient, in order to restore balance of functional mitochondria versus mutated mitochondria.
MPC-06-ID: Mesoblast is an Australian stem cell therapy company that focuses on allogenic mesenchymal stem cells to treat a number of different diseases, such as degenerative disc disease, a condition that is very common and progresses with age (1/3 or more of men and women between the ages of 40 – 59 have evidence of this condition).
During their phase 3 trial (Trial link), in completion by March 2021, they hope that the signalling factors that the stem cells release, will reduce inflammation and possibly induce regeneration of the disc and reduce low-back pain.
SRK-015: Scholar Rock is attempting to treat Spinal Muscular Atrophy, a genetic disease that affects the survival of motor neurons, by inhibiting the latent form of myostatin — a protein that inhibits muscle growth —by using a monoclonal antibody. They hope to counteract the muscle atrophy from lack of central nervous system signalling, with chemokine signalling that activates muscle growth. Phase 1 / 2 trial, completion April 2021, Trial link.
SkQ1 – Mitotech is an anti-aging company that develops therapies that protect the mitochondria from reactive oxygen species (ROS), such as SkQ1 an anti-oxidant that can easily penetrate the mitochondrial membrane where it can inhibit ROS and prevent dry eye. In particular, SkQ1 protects cardiolipin, an important protein found in the inner mitochondrial membrane. Their phase 3 trial, in completion October 2020, can be found here link.
Longeveron Mesenchymal Stem Cells (LMSCs): Longeveron is a stem cell company that develops therapies for age-related disease such as frailty syndrome, an age-related condition that hinders physical function and also increases the risk of injury. Frailty is highly correlated with mortality and is believed to affect 7 – 12% of people over the age of 65. To address this problem, Longeveron is developing an allogenic mesenchymal stem cell therapy infusion (Trial link, completion July 2021) that they believe stimulates endogenous tissue repair and reduces inflammation.
Mesenchymal progenitor cells: Cellular Biomedicine Group is another allogenic mesenchymal stem cell company — with an operation focused on the Chinese market —that they are using mesenchymal stem cells derived from human adipose tissue (fat) to treat Osteoarthritis (knee). Their phase 2 trial (Trial link) in completion by January 2022, is aiming at stimulate self-repair and reduce knee inflammation.
Nicotinamide riboside: ChromaDex is the leading provider of phytochemical reference standards, botanical reference materials and research grade materials for the natural products industry.
In their phase 1/2 trial (completion by December 2021Trial link) nicotinamide riboside — a precursor to NAD+ a crucial coenzyme required for many cellular processes, including the function of sirtuins that repair DNA strand breaks — is being used to test its potential properties counteracting the biological aging process. They are measuring hospitalization duration (Time to recovery) for patients with tissue damage (inflammation, acute illness) after nicotinamide riboside treatment. Right now more than 50 trials are testing NAD+.
Thanks for reading.
*Disclaimer: This information is for educational purposes only.