Novartis found that giving low doses of a drug called everolimus to people over 65 increased their response to flu vaccines. It did, by about 20 percent. Yet behind the test was a bigger question about whether any drug can slow or reverse the symptoms of old age. Novartis’s study on everolimus, which looked at whether the immune system of elderly people could be made to act younger, has been called the “first human aging trial.”
RAD001 (everolimus) also appeared to broaden the serologic response, causing enhanced seroconversion to heterologous influenza strains not in the chosen influenza vaccine. This finding is also suggestive of enhanced protection against influenza illness. Unlike the study with rapamycin administration in aging mice, no increase in naïve lymphocytes (no cancer concerns) was detected in humans.
Other clinically approved drugs have been linked to lifespan extension and protection against age-related diseases in animal models, including metformin and NSAIDs that have been prescribed millions of people. A recent retrospective examining patients with type 2 diabetes compared the effects on mortality rate of patients taking metformin or sulfonylurea monotherapy. Not only did patients taking metformin have a lower mortality rate than those taking sulfonylurea, they had a lower mortality rate than other patients seeing the same doctor who did not have a diagnosis of metabolic syndrome. While there are caveats with any study of this nature, the findings suggest that metformin may be affecting basic aging processes that underlie multiple chronic disease and not just type II diabetes. One wonders whether many of the drugs used to treat early stage chronic disease may be effective at least in part because they target the biggest risk factor for these diseases: aging itself.
Last week a Boston company, PureTech Health, said it was licensing two drug molecules, and the right to use them against aging-related disease, from Novartis and making the research the basis of a startup company, resTORbio. The company says it will further test whether such drugs can rejuvenate aged immune cells.
The immune-enhancing potential of mTORC1 inhibitors has been explored in a Phase 2 program at Novartis that included two successful Phase 2a studies in hundreds of elderly patients. Results will be detailed in an upcoming peer-reviewed publication. The results of these studies form the foundation for further clinical development in immunosenescence and other aging-related diseases by targeting the mTOR pathway.
The drug Novartis tested is a derivative of rapamycin, a compound first discovered oozing from a bacterium native to Easter Island, or Rapa Nui, and named after it. Thanks to its broad effects on the immune system, rapamycin has already been used in transplant medicine as an immune suppressant and a version is sold by Novartis as the anticancer prescription Afinitor.