An Update on a Human Telomerase and Follistatin Gene Therapy

Bioviva didn't succeed as originally envisaged, as a vehicle to bring human telomerase and follistatin gene therapy to the clinic; a recent article gave an outline of this history. At the moment I think few people are working on follistatin delivery, more is the pity, and the telomerase gene therapy banner has been taken up by another group. The original volunteer test subject, Liz Parrish, continues to perform a public service by publishing data on the outcome of her gene therapy - though I have to say that average telomere length as presently measured in sample of white blood cells is just about the least interesting of any measure one might propose to take following gene therapy with telomerase and follistatin.

Telomerase acts to lengthen telomeres, but average telomere length in immune cells is a terrible metric for age and tissue status. Average telomere length is an outcome of the pace at which cells are created from their stem cell populations, fresh with long telomeres, and the pace at which they divide, losing a little telomere length each time. In immune cells these behaviors are highly variable, greatly influenced by many transient health and environmental circumstances that have little to do with aging. Study after study shows immune cell telomere length to have a very poor correlation with age and age-related disease.

So instead, how about metrics of stem cell activity, or immune function, for example? The rationale for telomerase gene therapy is largely that it increases stem cell activity in tissue maintenance, and since it also reduces cancer risk in mice, one might suspect it is improving the ability of the immune system to destroy cancerous cells. Average telomere length on its own is interesting, but it cannot be used to claim rejuvenation, as is done here. It is too disconnected from meaningful metrics of aging, those that are actually closely tied to function and damage.

Before I underwent the therapy procedure, my white blood cell telomeres were measured in September, 2015 by SpectraCell's Texas laboratory, using a blood sample. They were determined to be unusually short, meaning that I was aging much faster than others my age. According to my telomeres, I was supposed to be in my mid-sixties. In March 2016, my telomeres were again measured by SpectraCell. I had already started at a disadvantage, which multiplied the anticipation anxiety. Thankfully, the results exceeded all my expectations. They showed that my telomeres had been extended from an initial 6.71kb to 7.33kb, meaning that my cells grew younger by about 20 years in only 6 months. The gene therapies had restored my telomeres in these cells to my normal age.

I hardly dared to hope there was room for improvement still. In 2018 I went again for testing at SpectraCell. My telomeres further increased from 7.33kb in 2016 to 8.12kb in 2018, equivalent to another decade of cellular rejuvenation. This outcome has exceeded all my expectations. First, because there have so far been no negative effects of my therapy. That is, no cancer, the alleged danger with activating the telomerase enzyme. But second, because my telomeres have continued to get longer without any additional treatment.

The same improvement was obtained following the muscle deterioration treatments: not only did my muscle mass increase after the myostatin inhibitor therapy, but continues to be robust 3 years after it took place. From pre-treatment to post treatment a growth in overall muscle mass and a reduction of intramuscular fat content was observed over a period of three years. This loss of intramuscular fat, also known as 'marbling', is associated with beneficial metabolic changes and improved musculature. My overall body weight did not decrease during this period. As my personal experience shows, a single treatment stimulated the telomerase and the myostatin inhibitor enzymes for at least 3 years after being administered, with no adverse effect. This can be a proof of concept that these two therapies, amply tested in animal models, are safe and efficient in humans.



While telomeres extension therapy will be very useful in the future, for the moment I see it bringing only marginal improvement. Especially with Liz. Probably 95% of the physical improvement is because of the myostatin inhibitor therapy, which increase the muscle mass and quality. What is a good news is that neither of the therapies had any adverse effects. That alone speeds the progress in the field by a few years. So she had shaved about 5-7 years of a couple of decayed worth journey. We are still far from a practical treatments but closer nevertheless. I'll for people under 60 probably the myostatin inhibitor therapy, is a quick win. Especially, if coupled with senolitic therapies.

Thelomere extending starts getting useful after 60, unless you have a special condition. The good news is that it doesn't hurt. At least in the short term....

Posted by: Cuberat at August 27th, 2018 7:30 AM

I very much hope inside a decade (if not 5 years) we can do both Telemeres extension and Senolitic therapies via medical tourism and cost being minimal. Hopefully, these two will provide us up to 10 years additional life, buying us more time for additional therapies to come online.

Really glad to see progress in these two areas and getting close to or in clinical studies. I just wish the same could be said for other rejuv treatments.

Posted by: Robert at August 27th, 2018 12:31 PM

Hi Robert,
It depends how you define medical tourism.. and how much risky and unproven treatments you are willing to get. After all, we have at least one person having dinner telomeres extension and myostatine inhibition therapies. So a guerilla style clinics pribavly already exist even for now. Albeit, they are not mass marketed not they are . Of course the therapies are extremely risky and unproven too.

Dasatinib+quercétin thérapies, the other hand, are so easy to do. Das is a bit pricey of you have to obtain it trough the established medical channels. But the senolitic dose is probably less than the daily intake of a cancer patient. The good thing is that dasatinib has well known side effects and dosage tolerance. The only problem is that we don't know how well could it work for humans. I don't see the tabloids pitching stories of people getting and looking younger after chemo. And I would expect to see at least a few cases given how widely dasatinib is used. So I don't expect as spectacular results in humans as we have witnessed with the mice.
I wouldn't be surprised at all if many cancer patients on dasatinib take quercétin as supplement. And yet there's not a single story...

I am more hopeful of Oisin platform. It is more targeted with gate side effects. It is more expensive and hard to copy by pirate clinics, though. And they will try to avoid the bad press until the human trials are fine and or had been proven to be safe and effective in humans.

Posted by: Cuberat at August 27th, 2018 12:57 PM

Totally agree we need a much better metric to judge the success of telomerase therapy than leukocyte telomere length. Still, it is encouraging that a woman who travels constantly and who doesn't have time to exercise, three years later still has a better balance between immune cell creation and destruction than she did before the treatment.

I wonder how long the plasmid could survive in the original cells it infects? If any hematopoietic stem cells were infected then some of them might continue to express the plamid telomerase for some time, as when they divide, even asymmetrically, there is a 50% they'll end up with the plasmid.

Telomerase therapy is available now, probably at extortionate cost, either here through Liz's associates:

or here:

or, in a couple of years Michael Fossel is using this therapy in a Phase I FDA Clinical trial from Alzheimer's:

Posted by: Mark at August 28th, 2018 5:11 AM

@Cuberat, I believe some preliminary results for Dasatinib are being reported at RAADFest this year.

Posted by: Mark at August 28th, 2018 5:12 AM

cannot find any sturdy or results in humans.

Posted by: cuberat at August 28th, 2018 2:15 PM

@Cuberat - there are none!

Posted by: Mark at August 29th, 2018 2:59 AM

Exactly. Not even metastudies,which would be not so hard to do. And it is a bit disconcerting and makes me skeptical on the das+qc approach...

Posted by: cuberat at August 29th, 2018 11:37 AM
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