Cheng Fang, PhD, Annovis Bio, Berwyn, PA, explains the unique mechanism of action of investigational small molecule, buntanetap. Buntanetap is an orally available agent, acting as a translational inhibitor of neurotoxic aggregating proteins. It acts on the iron response element in the 5′-untranslated region of mRNA that is preserved among neurotoxic aggregating proteins. Buntanetap increases the affinity of iron regulatory protein 1 (IRP1) to IRE, preventing association with the ribosome and thus, inhibiting translation. Buntanetap has been shown to inhibit the translation of multiple neurotoxic proteins such as amyloid precursor protein, tau and alpha-synuclein. In preclinical models, buntanetap was able to restore axonal transport, lower inflammation and protect against cell death. Its mechanism of action makes it a promising candidate in several neurodegenerative diseases where toxic protein aggregation and accumulation is at play. It is currently being developed for Alzheimer’s disease (AD) and Parkinson’s disease (PD), showing improvement in cognition in patients with AD and motor function in patients with PD in Phase II studies. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.
