Michael Fossel Michael is President of Telocyte

October 10, 2017

Should everyone respond the same to telomerase?

A physician friend asked if a patient’s APOE status (which alleles they carry, for example APOE4, APOE3, or APOE2) would effect how well they should respond to telomerase therapy. Ideally, it may not make much difference, except that the genes you carry (including the APOE genes and the alleles for each type of APOE gene, as well as other genes linked to Alzheimer’s risk) determine how your risk goes up with age. For example, those with APOE4 alleles (especially if both are APOE4) have a modestly higher risk of Alzheimer’s disease (and at a lower age) than those with APOE2 alleles (expecially if both are APOE2).

Since telomerase doesn’t change your genes or the alleles, then while it should reset your risk of dementia to that of a younger person, your risk (partly determined by your genes) would then operate “all over again”, just as it did before. Think of it this way. If it took you 40 years to get dementia and we reset your risk using telomerase, then it might take you 40 years to get dementia again. If it took you 60 years to get dementia and we reset your risk using telomerase, then it might take you 60 years to get dementia again. It wouldn’t remove your risk of dementia, but it should reset your risk to what it was when you were younger. While the exact outcomes are still unknown, it is clear is that telomerase shouldn’t get rid of your risk, but it might be expected to reset that risk to what it was several years (or decades) before you were treated with telomerase. Your cells might act younger, but your genes are still your genes, and your risk is still (again) your risk.

The same could be said for the rate of response to telomerase therapy. How well (and how quickly) a patient should respond to telomerasse therapy should depend on how much damage has already occurred, which (again) is partially determined by your genes (including APOE genes and dozens of others). Compared to a patient with APOE2 alleles (the “good” APOE alleles), we might expect the clinical response for a patient with APOE4 alleles (the “bad” APOE alleles) to have a slightly slower respone to telomerase, a peak clinical effect that was about the same, and the time-to-retreatment to be just a big shorter. The reality should depend on how fast amyloid plaques accumulates (varying from person to person) and how fast we might be able to remove the plaque (again, probably varying from person to person). The vector (slope of the line from normal to onset of dementia) should be slightly steeper for those with two APOE4 alleles than for two APOE3 alleles, which would be slightly steeper than for two APOE2 alleles. Those with unmatched alleles (APOE4/APOE2) should vary depending upon which two alleles they carried.

To give a visual idea of what we might expect, I’ve added an image that shows the theoretical response of three different patients (a, b, and c), each of whom might respond equally well to telomerase therapy, but might then need a second treatment at different times, depending on their genes (APOE and other genes) and their environment (for example, head injuries, infections, diet, etc.). Patient c might need retreatment in a few years, while patient a might not need retreatment for twice as long.

 

6 Comments »

  1. By the way, although Michael Fossel is obsessed with telomerase, he himself (although he is already 67 years old) unlike Liz Perrysh does not do any genetic experiments on himself, although he calls on others. Why? Because he knows more about telomerase than Liz Perrysh.
    It is known that telomerase is usually activated in oncology. Man, elephant, whale and other long-living species have short telomeres, which protects them from cancer, unlike mice – in which telomeres are longer than us, and life is 20-30 times shorter (including due to cancer).
    In brain cells, which rarely divide the length of telomeres remains almost the same in old age, but dementia develops precisely in them.

    Comment by Dmitry Dzhagarov — November 4, 2017 @ 8:16 am

  2. Actually, while telomerase is activated in the majority (approximately 90%, depending on the series) of human cancers, telomerase does not cause cancer and is generally protective against both mutations and clinical cancer. In regard to dementia, while most neurons do not divide in the adult human (or most other animals), microglia divide regularly and microglial cell senescence results in the pathology underlying human AD. Neurons are the “innocent bystanders” to glial cell dysfunction, much as cardiomyoctes (which rarely divide) are the innocent bystanders to the cell senescent changes that occur in coronary endothelial cells.

    Comment by admin — November 21, 2017 @ 10:59 am

  3. So Libella Gene Therapeutics are in the 1st phase with their clinical study with the gene therapy from Bill Andrews but i’m unsure if they’re targeting the Alzheimer’s as it might seem from their website. http://www.libellagenetherapeutics.com/ Any take on this Michael?

    Comment by Peter — November 20, 2017 @ 12:49 pm

  4. Our understanding from their website is that Libella does not have and is not seeking FDA approval. The Telocyte human trials will be in the United States, will have FDA approval and an IND, will have formal ethical review and approval from an IRB (institutional review board) at an academic center, and will not charge patients for our therapy.

    Comment by admin — November 21, 2017 @ 11:06 am

  5. I was wondering if Bill Gates might be interested in your approach as a moonshot for curing Alzheimer’s, given he is getting into this space?

    Of course there must be a great many people trying to get money from him, so not an easy ask…

    Comment by Mark — November 21, 2017 @ 10:59 am

  6. @Dimitry, I think only Michael Fossel knows what Michael Fossel would do if telomerase therapy was available today. I myself would not want extra copies of HTERT placed in my genome, which might be permissive of cancer, but this is not what Telocyte are planning, I believe – rather it’s a temporary expression of telomerase to return telomere lengths to youthful levels (when Cancer if rarer), after which normal shortening will gradually reoccur. Correct me if I am wrong, Michael.

    Comment by Mark — November 23, 2017 @ 6:37 am

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