If scientists can use geroprotectors to extend lifespans of model organisms and translate the effect to humans, then the appearance of many age related diseases should be slowed down explains Dave Schubert head of Salk’s Cellular Neurobiology Laboratory.
Chemical compounds found in Fisetin and Curcumin were synthesized into 3 AD drug candidates based on ability to protect neurons from multiple associated with the aging brain. CMS121, CAD31, and J147 as well as curcumin and fisetin were then shown to reduce the molecular markers of aging, dementia, and extend median lifespan of mice and flies.
The molecular pathway engaged by these AD drug candidates were demonstrated to be the same as 2 other synthetic compounds that are known to extend lifespans of many animals. Based on this and results of previous studies the team concluded that CMS121, CAD31, J147, curcumin, and fisetin all meet definition of being geroneuroprotectors, as published in the journal Trends in Pharmacological Sciences.
The team is now focussing on getting 3 GNPs into human clinical trials; first the fisetin derivative CMS121 currently in animal toxicology trials required for FDA approval; and then the curcumin derivative J147 which is under FDA review for allowances to possibly start AD clinical trial in 2019. Biochemical markers for aging will be incorporated into the clinical trials to assay for potential geroprotective effects.
Curcumin and fisetin are natural products that have been found to be GNPs which are already commercially available as supplements which may provide some therapeutic benefits now. Other studies being conducted may determine whether these compound have effects outside of the brain, if they benefit other body systems they could be used in additional ways to treat and/or prevent age related diseases.
Discovery of these candidates validates the discovery model developed by the team as plausible method for identifying additional compounds to promote healthy aging, which in turn may accelerate the pipeline for drugs to treat age related disease with no known cures.
