CuATSM is a small molecule drug sponsored by the company Collaborative Medicinal Development (CMD) that completed enrollment of a Phase 1 trial in Australia in June 2019. Originally used as an imaging agent in Asia, CuATSM has shown potential to treat copper zinc superoxide dismutase (SOD1) ALS.
In healthy SOD1 proteins, zinc maintains the protein’s shape and copper is essential to its antioxidant function. SOD1 mutations, though, can cause proteins to become unmetallated, meaning they release their necessary zinc and copper components and can no longer sustain cellular health.
Scientists hypothesize that CuATSM could act as a ‘copper chaperone’, delivering copper ions back into SOD1 proteins and enabling proper cellular function. CuATSM may also prevent protein misfolding and buildup of peroxynitrite, a molecule that can disrupt the electron transport chain in mitochondria.
The University of Melbourne and Oregon State University have completed studies that demonstrate significant improvements in lifespan in SOD1 mice treated with CuATSM. Additional tests at ALS TDI in 2016 confirmed the drug’s efficacy in SOD1 mouse models. Positive results at multiple labs have increased confidence in CuATSM as it goes forward into clinical trial.
The Australian Phase 1 trial has so far shown promise in people with both sporadic ALS (sALS) and familial ALS (fALS). However, the trial size in this study was small, involving just six people with ALS.
Further clinical development in Australia will be dependent on demonstrated success at this early stage. There are currently no CuATSM trials planned in the U.S, but ALS researchers expect results from the Phase 1 trial in Australia in April 2020.