Saw this on a recent email discussion list I am on. Rapamycin is the best longevity deal out there, and likely will be the best for the next decade or two…
Following our last GRG Zoom meeting I tried to follow up with regard to
the various gene therapies discussed. These included the gene therapies
for dementia, sarcopenia and telomere attrition.
The results were sobering. Costs range from $250 000 to $700 000, with
most of that money going to patent fees. Even medical tourism does not
reduce the price significantly.
The only light in the tunnel was that the AAV vectors go off-patent in
2023 and 2024. Does anybody know of any group planning to provide
cheaper gene therapies in the foreseeable future?
From this group, but website no longer maintained and email discussion group not very active:
Has anyone tried Integrated Health System’s follistatin gene therapy? What does it cost? If effective, it would certainly increase healthspan, but the effect on lifespan is unknown. They also offer telomerase induction therapy, but I have no idea what that involves.
I’m confused about the “duration of effects is 2 years” comment.
If what they are doing is truly gene therapy, and the are getting integration into the genome / transfection of the gene, it doesn’t seem like there should be a “duration” limitation. That is sort of the key benefit of gene therapy; its a permanent fix (or so I thought).
Does anyone here have more information on what exactly they are doing, and why it would only be effective for two years? I know they say they are using plasmids in the process.
I must admit I agree that the statement of having effects for two years sounded odd. I am not enthused by some of these gene therapies as they seem to potentially cause more problems than they solve.
I’ve asked the Bing AI which uses GPT 4 two questions regarding this. Don’t take this as absolute fact because I’ve known it to make a lot of errors but I think it gives a pretty good answer on the mechanism of why this is the case. This is why I think AAV vectors might be the go to and as you mentioned the patent expires 2023/2024 and offers a more permanent solution.
Interesting information coming out of GPT4, thanks for posting. I wouldn’t trust it on any single detail, but the general information is probably reasonably accurate.
Perhaps its a reasonable start for longevity gene therapies…if they are only temporary fixes.
Permanent changes this early in the world of gene therapy, unless used in serious, fatal diseases, seems like it may be ill-advised. The AAV vector is a non-targeted vector I believe, so the risk of off-target effects (being inserted into the middle of an otherwise fully functional gene) can mess with things, and may be impossible to correct.
MIT tech review has an article on the Minicircle attempt. Setting aside the issues of whether this effects aging per se, what evidence is there that plasmids are even an efective approach in humans?
I agree errors could lead to unforseen consequences. I saw a video with David Sinclair and although I largley believe he is a grifter for resveratrol and NMN he was talking about a type of gene therapy that can be induced or reversed using antibiotics. The hypotheitcal situation he used was a person got into a car accident and they take antibiotic to active dormant healing genes. He also mention taking the antibiotic to silence them again. With things like crisperoff and new varaints of gene editing technique I think it will be safer to edit the genome permantly if there is a kill switch. But as you said its early in gene editing so who knows how long till these methods are practical.
Good point. yes - I’ve done work in a gene therapy startup. The area of inducible / conditional expression of specific genes that you insert into an organism is a well-proven and frequently used approach in animal model development. You can insert genes into mice, for example, that get “turned on” when exposed to tetracycline. This allows you to turn on, and turn off that gene in question whenever you want. I suppose you could take that approach in humans, but the entire medical system is going to have to move along with this as there is the risk of someone accidentally turning on specific genes in someone who has had this type of gene therapy (when, in a hospital, for example, someone gives a patient tetracycline for other purposes).
Just finished watching it.
Apparently the Phase 1 Trials have concluded in August 2023. Does anyone have access to the results? I couldn’t find them on the website.
I can also try contacting them.
I’d like to hear more about AAV going off-patent. Do we have any intel on how much of the very expensive gene therapy prices are due to that? As things are going, I think I will pay 25k to get the FST in Feb, both to test that I personally have no adverse reaction, and to buy me a year of effects while AAV hopefully goes off patent and comes down in price.
so the risk of off-target effects (being inserted into the middle of an otherwise fully functional gene) can mess with things,
Im no expert on how this works, but on my call with Dr Sewell of Ingetrated Health, he said some of the DNA does make it into the nuclues (which is important for the therapy to work), but it doesn not get included into our chromosomes. I asked GPT to elaborate:
“In most cases, AAVs do not integrate their genetic material into the host’s genome. Instead, the AAV DNA exists as independent, circular episomes (extrachromosomal DNA) in the nucleus. This reduces the risk of disrupting the host’s genes, which can lead to cancer or other unintended consequences.”
I followed up, asking:
Can AAV gene therapy occasionally get incorporated into our chromosomes and disrupt an existing gene?
ChatGPT: Yes, AAV gene therapy can occasionally result in the integration of the therapeutic DNA into the host’s chromosomes, though this is relatively rare compared to other viral vectors. Here’s how and why this might happen:
Integration Mechanism:
Random Integration: While AAVs are primarily episomal and do not actively integrate into the genome, random integration events can occur at a low frequency. This happens when the AAV DNA inadvertently becomes inserted into the host’s genomic DNA due to cellular DNA repair mechanisms or other processes.
Site-Specific Integration: AAVs can also integrate at specific sites. For example, integration into the AAVS1 site on chromosome 19 is well-documented. This site is considered a ‘safe harbor’ as it’s less likely to disrupt essential genes or regulatory elements.
Disruption of Existing Genes:
Insertional Mutagenesis: If AAV DNA integrates randomly into the genome, it can potentially disrupt existing genes or regulatory elements. This disruption can lead to a loss of function of the affected gene or unintended consequences like the activation of oncogenes or inactivation of tumor suppressor genes.
Consequences: The consequences of such disruptions depend on the function of the affected gene and its role in cellular processes. In some cases, it could lead to cellular dysfunction, disease, or cancer.
Factors Affecting Integration:
Cell Type: Some cell types may be more prone to integration events than others. For example, dividing cells might present more opportunities for integration due to the dynamic nature of their DNA.
Vector Design: The design and serotype of the AAV vector can influence its integration profile. Researchers are continually working to design vectors that minimize the risk of harmful integration.
Summary:
While AAV gene therapy has a lower propensity for integration compared to other viral vectors, it can occasionally integrate into the host’s chromosomes and potentially disrupt existing genes. This rare event is a consideration in the risk-benefit analysis of AAV therapies, and ongoing research and monitoring are aimed at understanding and mitigating this risk. As with any medical treatment, the potential for adverse effects is weighed against the therapeutic benefits, particularly for serious or life-threatening conditions where few other treatment options exist.
