Boston- and Atlanta-based clinical-stage pharmaceutical company Inhibikase Therapeutics, Inc. published the biochemical rationale for potentially treating Parkinson’s disease with IkT-148009, a highly selective Abelson Tyrosine Kinase (c-Abl) inhibitor.

Misfolded, aggregated alpha-synuclein is a primary target for the development of disease-modifying therapies for Parkinson’s disease. Recent research in animal models has demonstrated that the presence of misfolded alpha-synuclein alone isn’t enough to initiate Parkinson’s disease. The study authors posit that when misfolded alpha-synuclein enters a neuron, it activates c-Abl, which converts the protein to a toxic form, and it’s this toxic form that is hypothesized to be responsible for the neurodegeneration that occurs in Parkinson’s disease.

Nilotinib, a c-Abl inhibitor indicated for the treatment of certain types of cancer, has also been studied as a treatment for Parkinson’s disease, but failed to show a clinical benefit. However, the fact that nilotinib doesn’t accumulate at high enough concentrations in the brain to inhibit c-Abl may explain these results.

In animal models, IkT-148009 demonstrated the ability to clear alpha-synuclein aggregates from the brain and gastrointestinal tract and restore motor and non-motor functions. The compound is currently in a Phase 1b extension study—with results expected in the spring or summer of 2022—that will help evaluate its safety, tolerability, and effect on motor and non-motor symptoms of Parkinson’s.