Libella Gene Thereapeutics Moving Ahead with a Small Phase 1 Trial of Telomerase Gene Therapy

Libella Gene Therapeutics is developing telomerase gene therapy as a clinical treatment, work that results from more than a decade of studies in mice that show extended life, reduced cancer risk, and improved health. Telomerase acts to lengthen telomeres, the repeated DNA sequences at the ends of chromosomes that shorten with each cell division. Average telomere length in the somatic cells making up any given tissue is a function of the rate of cell division versus the pace at which stem cells produce new daughter somatic cells with long telomeres. Since stem cell activity declines with age, it is no surprise to see telomere length shorten.

Telomerase gene therapy acts in part by extending the working life of somatic cells, and thus the prospect of active cells, burdened with damage due to a longer working life, and the attendant cancer risk has always been a concern. That telomerase gene therapy reduces cancer incidence in mice may be the result of improvements in immune function, particularly cancer immunosurveillance, that outweigh any increase in cancer risk due to increased activity of damaged cells. Mice and humans have very different telomere dynamics, however, so it remains to be seen whether or not the same balance of outcomes is the case in our species. The best way to find out, as ever, is for brave volunteers to try the therapy.

The clinical trial (NCT04133649) has just began recruitment stage. The procedure will consist of a single intravenous injection, followed by six safety and efficacy evaluations. 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).

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.

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




- Not approved by FDA

- Location Zipaquirá, Cundinamarca, Colombia

- Using for promotion

This is that Liz Parrish style junk all over again

This is the swill that will bring the whole longevity biotech image down the drain

Posted by: Bill Comparte at October 24th, 2019 6:06 AM

Well, funding is difficult, and if they have to do it in a third country I think that's great. At least somebody is doing something and not sitting on their hands; we need to iron out exactly what telomerase induction will do - hopefully it won't just leave the host cancer - riddled.

The financial and other barriers the FDA puts up are enormous...

Posted by: bmack500 at October 24th, 2019 10:23 AM

I had the privilege of briefly speaking to Liz Parrish at Raadfest recently. She looked very healthy and at 48 looked to be 24. Cosmetic treatments can improve appearance but can never actually make someone 48 look honestly 24. I mention this because what's on the outside can possibly reflect the health that's inside. Thank goodness brave researchers can escape the FDA mud bog and move forward much faster outside the United States.

Posted by: August at October 24th, 2019 11:17 AM

"This is the swill that will bring the whole longevity biotech image down the drain"

If it fails yes, and especially if there's severe adverse events. The lack of a placebo control is also problematic, and the study as a whole is underpowered even for a phase I. While the FDA is not perfect, the strict requirements it imposes exists for a reason, one of which is to ensure that trials are actually capable of detecting the anticipated effect.

Posted by: Dylan Mah at October 24th, 2019 11:37 AM

Why they are doing this in Columbia is Obvious to me. Is it even possible for the average person ( in a US Court) to give informed consent to Gene Therapy? I think not.

Brave Volunteers? Well I bet there is a substantial financial incentive.

Posted by: JohnD at October 24th, 2019 4:56 PM

Or a person could increase telomerase for pennies a dose right now with low-dose fluvastatin and valsartan. This study is in humans.

"In the present study, we showed that low-dose fluvastatin and valsartan in combination significantly increased the expression of several important longevity genes (SIRT1, PRKAA, KLOTHO). Moreover, these changes correlated with an improvement of functional and structural arterial wall characteristics as well as with telomerase activity, both assessed previously [7,8,9,10]."

Posted by: Lee at October 24th, 2019 5:27 PM

Gene therapy is ridiculously expensive, but the studies on the benefits of telomerase induction look pretty convincing. It remains to be seen what the relative effects are on somatic vs. progenitor cells but I expect general attrition would limit the concerns Reason has over extending the working life of somatic cells.

Posted by: Mark at October 25th, 2019 2:15 AM

As always, I wonder why the hell all this longevity experimentation takes place on mice. They're just so damn different from humans. We need to start using monkeys. Or, at least, cats and dogs. These advanced, large, similar-type mammals will give us much more information about how all these new longevity drugs and treatments will probably work in humans.

Posted by: Zan at October 26th, 2019 11:56 AM

Actually Zan, I don't think telomere dynamics are that different between mice and humans. Yes, mice don't erode their telomeres as far as humans do in a normal mouse lifespan, but they do lose telomere length, at an accelerated rate that corresponds well with their much shorter lifespans. So the important thing is the rate of telomere loss, not absolute length. The real reason mice studies don't translate to humans is mostly because the mice have been cured of a disease model that doesn't really model the disease, if you see what I mean.

Posted by: Mark at October 27th, 2019 12:38 PM
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