Telomerase gene therapy aims to delay aging

Clinical trial of telomerase treatment (NCT04133649) just began recruitment stage. The procedure will consist of a single intravenous injection, followed by six safety and efficacy evaluations. Its author, Libella Gene Therapeutics, declares:

The goal is to extend the telomeres to prevent, delay, or even reverse Aging.

Participants will receive adeno-associated virus (AAV) containing gene expressing telomerase reverse transcriptase enzyme. AAV is expected to move from the circulatory system to tissues, invade cells, and establish telomerase expression inside cells. Viruses will not modify the genome – AAV’s genetic material normally exists separately in the cell cytoplasm (as an episome).

There are two key aspects to consider the potential of this approach:

  • How efficient AAV will be in reaching organs crucial for aging and establishing telomerase expression inside cells? AAV reaches less than 0.2% muscle cells, including heart cells. Not all AAV serotypes cross blood-brain barrier and typically they require special optimization to spread through brain. For high efficiency we need high doses, but their upper range is limited by immunological reactions.
  • How efficient is telomerase expression in anti-aging approach? Experiments on mice show that telomerase can extend their median survival by 20%. However, those results are not consistent between species and therefore may not be extendable to humans. Recent thorough review of animal studies in longevity gave relatively little attention to the shortening of telomeres, arguing that multiple other mechanisms are more crucial in aging.

Formally, the study is phase I trial, which limits the main goal – whether it is successful or failed attempt – to safety only. In this case, the primary goal was declared as the incidence of adverse effects.

Determination of dosing and tolerability is an important first step in all gene therapies. High doses of viral particles result in significant immunological reaction. Moreover, liver damage is a common adverse effect in early gene therapies, because of liver’s participation in blood filtering. In addition, telomerase introduces additional risk on its own. In 85% cases of cancers, telomerase is found upregulated, which raises concerns about potential oncogenicity of AAVs with hTERT gene.

Secondary goals include measurement of telomerase activity, telomere length, and general physical exams.

The trial is accompanied by two similar phase I attempts (NCT04133454, NCT04110964), which target Alzheimer’s disease and critical limb ischemia.

According to third-party information, procedures will be conducted in South America:

Patients participating in the trial will be enrolled in their country of origin and will travel to Colombia. Patients will stay in Colombia for a few days while the treatment is administered and hospitalized for observation. Patients will then return to their country of origin and will be followed-up per the study protocol.

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