Michael Fossel Michael is President of Telocyte

August 10, 2017

Progeria and Telomerase

Recently, John Cooke at the Houston Methodist Research Institute, showed that telomerase, when expressed in cells from progeric children, caused a “substantial physiologically relevant and meaningful effect on the lifespan and function of the cells.” As many of you know, progeria is a disease in which young children appear old, with baldness and osteoarthritis, and usually die of advanced cardiovascular disease, such as heart attacks, typically around age twelve. In short, they appear to have extremely rapid aging. Cooke’s results suggested that telomerase might offer a therapy. Oddly enough, both Cooke and the media described this finding as “surprising”.

While these results are promising, they are hardly surprising. In 1996, I published a book going into this prospect in detail, then wrote the first medical papers on this the medical potential in JAMA in 1997 and 1998. This was followed up with a medical textbook which explored the entire area in 2004, and another book in 2015 that described the medical potential of telomerase. What is truly surprising is not the most recent results, but that anyone finds the results at all surprising.

While not actually surprising, they present a bitter irony, in that any number of deaths, including deaths of progeric children, might have been prevented and may still be prevented if we only understand and act upon what we have known for two decades and which Cooke’s results only highlight again.

The irony – and my exquisite personal frustration – is that I proposed this approach annually in our global meetings for progeric children, starting twenty years ago. For about a decade, beginning several years before the turn of the millennium, I had been part of the annual global reunion of progeric children. Each year, we gathered with perhaps three dozen progeric children and their families from around the world, giving them a chance to meet one another, to talk with experts, and … to feel normal among other children and families who had the same problems. In 1999, among those progeric children was a young boy, whose parents were both physicians, and who were desperate to find a cure for progeria. Although I explained the potential of using telomerase as an intervention, they founded the Progeria Research Foundation and aimed it solely at genetic markers rather than epigenetic intervention. They managed to get significant funding through the NIH, fund raising, and government contacts in order to fund a set of studies that localized the genetic error responsible for progeria. As I predicted, none of the subsequent therapies based on their approach have had any effect on the disease. Worse yet, and like all the other progeric children I have known over the years, their son died of progeria. Had we gone straight to telomere-based interventions rather than taking the detour, many progeric children – not merely their son — might have been treated more effectively.

John Cooke and his colleagues have done well to show that they can reverse the problems seen in progeric cells, yet others have gone further. Maria Blasco’s group, for example, has shown that she can not merely reset aging in cells, as Cooke’s group has, but can do the same in animals. Moreover, we are collaborating with her group to take this approach in our upcoming human clinical trials next year, initially aiming at Alzheimer’s disease.

The fact that this comes as a surprise, given what we have known about the potential of telomerase for more than 20 years is a tragic example of wasted opportunities, wasted funding, and wasted lives. Telomerase was shown to reverse aging in cells 20 years ago; telomerase showed its value in animals 5 years ago; Telocyte is ready to show the benefits of telomerase in human trials next year.

2 Comments »

  1. You’re a legend, Michael.

    Comment by qt3.14 — August 15, 2017 @ 12:20 am

  2. Progeric children can be prototype for general aging, in manner akin to various hypercholesterolemias in accelerated atherosclerosis with different clinical consequences. However I feel hard scientific evidence is lacking in the telomere science. For that we will need carefully crafted controlled trials in animals followed by in humans. Objectivity will come through labs, followed by translational and finally human trials.
    Though telomere shortening may well be an important pathway, or even a dominant one, one cannot brush aside others’ inputs. Nir Barzalai’s metformin study may be nearing completion. When results are out it may come with new surprises.
    No doubt our understanding on aging is incomplete. Many jigsaws are missing for sure. We all have tendencies to focus on our respective special fields, looking at elephant’s trunk, ears, legs etc, missing out on whole new animal. Bird’s eye view is as important for gathering whole picture.
    Most biotechs jump in at results merely at cellular levels. Most of them are bound to fail. Many scientists attracted grants, spent money and moved on to their next ventures. Many have indeed tried to sell ‘snake oils’.
    We expect a new edition of your textbook on Aging Dr. Fossel. Thirteen years is good amount of time to deserve update. A lot has happened during this. Some theories need debunking, as unlearning wrong stuff is as important to create room for new stuff.
    All the best!

    Comment by Kawal Preet Singh — August 20, 2017 @ 4:57 pm

RSS feed for comments on this post. TrackBack URL

Leave a comment

Powered by WordPress