O.25Phase 1 clinical trial of losmapimod in FSHD: safety, tolerability and target engagement

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression at the D4Z4 locus resulting in aberrant expression of the homeobox transcription factor DUX4. DUX4 expression activates its downstream transcriptional program resulting in cell death, skeletal muscle loss and progressive motor disability. Fulcrum Therapeutics is developing losmapimod to treat FSHD at its root cause by inhibiting DUX4 expression. Pre-clinical studies demonstrate that losmapimod is a potent and highly selective small molecule inhibitor of p38 α/β resulting in reduction of DUX4 activity and its downstream transcriptional program preventing cell death without impacting myogenesis.

Source: Neuromuscular Disorders - September 30, 2019 Category: Neurology Authors: M. Mellion, L. Ronco, D. Thompson, M. Hage, S. Brooks, E. van Brummelen, L. Pagan, U. Badrising, B. Van Engelen, G. Groeneveld, D. Cadavid Source Type: research