Neurology

Fruit fly studies suggest inhibiting FAK, integrin β, TLN1, TNS1 or MMP1 could help treat seizures. In a Drosophila model of mechanically induced seizures, an astrocyte-specific RNAi screen identified four genes encoding components of focal adhesion complexes -- FAK, integrin β, TLN1 or TNS1 -- as genes required for seizures. In a Drosophila model of chemically induced seizures, astrocyte-specific RNAi targeting FAK, integrin β, TLN1 or TNS1 decreased locomotion defects compared with no RNAi. Also in the model, astrocyte-specific RNAi targeting MMP1 -- an upstream mediator of integrin β -- or a tool compound MMP1 inhibitor decreased seizure-like behaviors and locomotion defects. Next steps could include identifying and testing FAK, integrin β, TLN1 and TNS1 inhibitors in models of seizure.

Pfizer Inc. and Verastem Inc. have the FAK inhibitor defactinib (VS-6063, PF-4554878) in Phase II testing for mesothelioma and non-small cell lung cancer (NSCLC), Phase I/II testing for ovarian cancer, Phase I testing for pancreatic cancer and solid tumors and preclinical testing for breast cancer...