Mansuo Hayashi, PhD
FRAXA Postdoctoral Fellow
FRAXA funded studies by Nobel Laureate, Susumu Tonegawa, investigating how the enzyme PAK regulates the shape and function of dendritic spines of neurons. Dr. Tonegawa’s team demonstrated that genetic reduction of PAK could rescue most signs of Fragile X in mice engineered to mimic the disease.
This essential proof of concept work was also the basis for a company, Afraxis. No specific PAK inhibitors existed at that time, so Dr. Tonegawa founded Afraxis to find useful drugs that inhibit PAK.
Results:
Rescue of Fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486
This paper, published in the Proceedings of the National Academy of Science, showed that FRAX486, an experimental compound developed by Afraxis, inhibits all the PAKs in the brain. It also reversed most of the important Fragile X animal model phenotypes with a single dose!
Genentech currently owns the rights to FRAX486 and related compounds developed by Afraxis.
