Therapeutics: Nicotinic acetylcholine receptor α7 (CHRNA7)

Rat and mouse studies suggest agonizing CHRNA7 could help treat traumatic brain injury (TBI) by decreasing damage to the blood-brain barrier (BBB). In a rat model of TBI, a CHRNA7 agonist tool compound decreased neutrophil recruitment to the brain, BBB permeability and plasma levels of the proinflammatory markers IL-1β and high mobility group box 1 (HMGB1) compared with vehicle. In a mouse model of TBI, a positive allosteric modulator (PAM) of CHRNA7 decreased BBB permeability. Next steps could include testing CHRNA7 agonists and PAMs in other models of brain inflammation.

Bayer AG, Forum Pharmaceuticals Inc. and Mitsubishi Tanabe Pharma Corp. have encenicline (EVP-6124; MT-4666), a CHRNA7 agonist, in Phase III testing to treat Alzheimer's disease (AD) and schizophrenia. ...