I submitted a proposal to ITP this year, and received feedback. I’ll share the comments here and would love to hear other people’s feedback from their ITP submissions.
“The C2024 ITP proposals have been reviewed by the ITP Access Panel and Steering Committee. Regrettably, the combination of rapamycin, trametinib, and lithium was not prioritized to move into pilot studies for Phase I testing. Some of the reviewers’ comments were as follows:
While the rationale for testing rapamycin and trametinib is strong, the reasons for selecting lithium are less clear. The application states that lithium can extend lifespan in mice but no reference is provided. Nespital et al. reported in Aging Cell in 2021 that “lithium can mildly increase health during aging but not lifespan in mice.”
Several statements require clarification. Why is it recommended to start the treatment at 7-9 months of age? Periodic blood tests are suggested as a method for monitoring effectiveness of the treatment but it is not stated what is to be measured.”
@Olafurpall I just noticed on your substack that you had also submitted an ITP proposal on once weekly rapamycin. Did you get any feedback different than the one above?
"The C2024 ITP proposals have been reviewed by the ITP Access Panel and Steering Committee. Regrettably, intermittent rapamycin was not prioritized to move into pilot studies for Phase I testing. Some of the reviewers’ comments were as follows:
Intermittent rapamycin has already been shown to extend lifespan of different mouse strains using a variety of intermittent dosing regimens, including the 1x/5 days dosing strategy proposed here, and to have reduced metabolic side effects relative to daily/continuous rapamycin treatment.
The most important questions surrounding intermittent use of rapamycin in mice are not addressed: 1) what is the efficacy of intermittent rapamycin vs. continuous rapamycin – are the benefits as well as the risks much lower; and 2) what is the optimal intermittent rapamycin dosing regimen. The first of these could be addressed by the ITP, the second would require detailed healthspan analysis and is outside the scope of the ITP.
If you are able to fully address the concerns stated above, you are welcome to resubmit you application for consideration another year. The resubmission should include responses to the comments and questions from the reviews and an explanation of how the application has been modified and strengthened. The next submission deadline is February 28, 2024."
The study they are referring to when they say that rapamycin has been found to increase longevity at a dosing regimen of once every 5 days is most certainly this study. Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice - PubMed Despite having read a ton of studies on rapamycin, I had somehow missed that study. The study does give some evidence of every 5 day dosing improving lifespan with potentially reduced side effects than daily dosing (this regimen did not impair glucose tolerance in the mice). It’s uncertain how this regimen compares to every day dosing when given orally starting at young ages. However, this study supports my hypothesis that the optimal dosing regimen for humans is not to take it weekly but somewhat less frequently but at higher doses.