Trials of Cell Therapies for Heart Regeneration

Stem cell therapies to repair heart damage were one of the first to become widely available via medical tourism, and have been underway in earnest for more than a decade now. There is evidence from their use that benefits can be attained for patients. Providers and researchers continue to refine their techniques. There are numerous studies. That evidence is not good enough for the conservative end of the scientific community, who require a complete and rigorous understanding of the mechanisms of action before proceeding with enthusiasm, and nor for regulatory bodies in the US and Europe. Thus trials continue, now into their late stages, and treatments remain unavailable in many countries:

Like any new branch of medicine, cardiac cell therapy has progressed in fits and starts. Despite dozens of clinical trials, there's no slam-dunk treatment for improving the cardiac function of heart failure patients, but marginal, statistically significant improvements observed in some of the studies are propelling the cell-based therapies to ever larger, more expensive, and more rigorous trials. Most cardiologists remain underimpressed, says the head of an ongoing Phase 3 trial in Europe that involves injecting bone marrow cells into heart attack patients. "If [the trial] is positive, that's great, but I still think we'll have quite a challenge to convince people. If it's negative, then you get most of the cardiac community saying, 'Yep, we expected that.'?"

Now, it's make or break. Some anticipate that the results of the trial and two other ongoing Phase 3s will finally provide definitive evidence supporting the efficacy of cell therapies for the heart - evidence that has so far been lacking. On the other hand, negative results could spell the end of the approach altogether. "If our Phase 3 doesn't work, I think there's little likelihood any program could succeed in this indication," says the CEO of a Belgium-based firm sponsoring a clinical trial involving bone marrow-derived cells. "In the event they don't work [this time], I think it will be the end."

The idea to pluck cells from a person's bone marrow and shoot them into the heart took root in 2001, when researchers showed that doing so in mice could help regenerate damaged heart tissue. Yet no one knew how the cells worked. At the time, the prevailing thought was that stem cells took up residence in the heart and proliferated to produce new tissue. But this idea has since become a matter of debate. While some researchers claim the cells can form new cardiac muscle, others assert that the cells only very rarely differentiate into cardiomyocytes and instead support cardiac regeneration by other means.

Many scientists now believe that the introduced cells perform a paracrine function, signaling the activation of reparative pathways via growth factors or other secreted messengers. On its own, the heart regenerates about one percent of its tissue per year via the division of cardiomyocytes; perhaps cell therapies simply boost that normal behavior. The absence of a concrete mechanism of action has been one of the main criticisms of the field. On the other hand, most patients don't care how a treatment works, just that it does. "We have more trials than we have meaningful basic science papers. You'd like it to be the other way round. But I understand why there was an explosion [of clinical trials] - because there is such a need." And many researchers disagree that a known mechanism is required for advancing the therapy. "Nothing moves a field forward like actual clinical trials." While mechanisms are important - knowing them can help optimize treatments, for instance - "you can't slow things down because the mechanism of action isn't agreed upon by everybody."

Link: http://www.the-scientist.com/?articles.view/articleNo/42842/title/Hearts-on-Trial/

Comments

REPLENISENS at work! And yet again we are dying waiting for cures because the FDA and EU bodies slow progress down to a virtual crawl. So many promising therapies and yet they languish in research limbo due to red tape. No surprise whatsoever to me that medical tourism bypasses this and will continue to rise as more biotechs take therapies with increasing evidence of effectiveness offshore.

Safety and Efficacy are important but there needs to be a balance between that and actually getting treatments and therapies to patients in a timely manner. An average of ten years for a new drug or therapy is a complete farce.

Posted by: Steve H at May 22nd, 2015 6:56 AM

I wonder what something like this would cost via medical tourism. I'd wager a decent amount since you're at the mercy of the limited availability and demand. Not to mention, as far as recent medical tourism goes, the vague reference of a "few hundred thousand dollars" for biovivas telomerase therapy seems like it would be rather steep. Not that it wouldn't be expensive in the US or EU, because it probably would...just a few thoughts.

Posted by: Ham at May 22nd, 2015 7:10 AM

Ham full body therapy from bioviva with TERT and Miyostatin Inhibtor would run you about $200k for a full body treatment. The problem is because they have yet to build their own lab, once they do so the price will be dramatically reduced. They are pushing to get the prices down as much as possible for the mass market.

Also Dr Fossel is also pushing for that same Telomerase gene therapy to go through the FDA under the project name TELOCYTE and I believe is working with Dr Maria Blasco from the CNIO. According to his blog they are applying for a new drug status and completing some remaining animal tests before moving to clinical trial.

As with anything new the price is going to be high until costs fall through demand and manufacturing improvements. The rich will most certainly be the guinea pigs for the masses with any therapy that's for sure.

Posted by: Steve H at May 22nd, 2015 8:46 AM

Yeah I know prices will fall eventually. I didn't know they had to build their lab and all that still. I read about dr. Fossel yesterday also. I agree that the rich will be guinea pigs at first, for sure. If I was older myself I'd consider it. I just hope some kind of meaningful longevity comes out of telomerase therapy. Some people seem high on it, others not so much.

Posted by: Ham at May 22nd, 2015 9:02 AM

Steve,

Please correct me if in wrong here, but from what I understand, Telocyte is a project towards curing Alzheimer's right? So wouldn't there be a difference between that and what BioViva is offering? Just wondering because you said Fossel was pushing the same therapy under the telocyte name to the FDA. I'm all for an Alzheimer's cure, just wanted to see if I'm missing something.

Posted by: Ham at May 22nd, 2015 9:55 AM

Ham,

Yes you are correct Telocyte is aimed at what he called the Golden standard and he wants to cure Alzheimers as his initial drive. However he goes on to say that the various aging diseases can be potentially mitigated through the same therapies but he wants to go for the big target as no one else has come close to a cure.

https://www.youtube.com/watch?v=wE9Hmbyt3qU

Regarding Bioviva, I know it is the same gene therapy (AAV) as I have been told by the CEO of the company it is. The important thing is in the Serotypes, Bioviva have a number of Serotypes that target different cell types. Dr Fossel will be targeting one type of cell but the therapy is the same which is hTERT.

Now given he is talking about it being able to help with the other aging diseases do you honestly think he will stop once he cures Alzheimers or do you think it will be used for off label use to tackle other aging problems?

Posted by: Steve H at May 23rd, 2015 5:36 AM

Gotcha. Yeah, I figured it would be a two birds with one stone type thing with Alzheimer's and aging together, since the FDA doesn't recognize aging as a disease yet... It would be for Alzheimer's with a potential effect on longevity. If he manages to cure Alzheimer's, or even has mild results with it, with longevity benefits I'm sure it would be widely used off label. Here's hoping.

Posted by: Ham at May 23rd, 2015 5:59 AM

Well as I understand it the Serotype used will determine the target cell types it effects so it would need a mixture of serotypes for whole body effect.

Bioviva are hoping to organize a pilot study with TERT before that hopefully working with Longecity. The plan is a limited pilot with TERT gene therapy most probably targeting an area of localized skin on a person.

I suspect we may see good results as does Dr Fossel and there is every reason so think it is a good place to intervene on aging. I know Dr Fossel has talked about other aging diseases and talks about reversing aging so to me it is obvious he plans to do more than just AL once he has the data.

Posted by: Steve H at May 23rd, 2015 7:59 AM
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