The Strategy of mTORC1 Inhibition Fails a Phase III Trial

The worst possible outcome when developing a clinical therapy is not an early failure. It is a late failure, in the final and most expensive phase III clinical trial, in which the therapy interacts with a sizable patient population, and after a great deal of time and funding have been devoted to the program. This result is far more likely for therapies based on mechanisms that have smaller rather than larger effect sizes, and where that smaller effect size varies from individual to individual for reasons that are not well understood - something that describes all too much of the past few decades of efforts to treat age-related disease. Unfortunately this worst case phase III failure just happened to resTORbio's mTORC1 inhibitor RTB101, in tests of its ability to improve immune function and reduce the burden of infection in later life. The inhibition of mTOR, and specifically only the mTORC1 protein complex in order to reduce side-effects resulting from inhibition of mTORC2, is one of a range of potential approaches demonstrated in animal models to modestly slow aging via upregulation of cellular stress response mechanisms. It affects some of the same processes as calorie restriction and exercise. Another way of looking at it is that it pushes metabolism into a state that makes it incrementally more resilient to the accumulated damage of aging. However, all such strategies examined to date perform far better in short-lived species than in long-lived species, a situation...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs