AMO-02 (tideglusib) is in development for the treatment of congenital myotonic dystrophy and has potential for use in additional CNS, neuromuscular and oncology indications. AM0-02 is positioned to enter clinical stage development for the treatment of the severe form of congenital myotonic dystrophy known as DM1 or Steinert disease. In cellular and animal models of DM1 and Duchenne muscular dystrophy, as well as in muscle biopsies from patients, activity of glycogen synthase kinase 3 beta (GSK3ß) has been shown to increase. Inhibitors of GSK3ß have been shown to correct the activity of regulatory proteins, such as CUGBP1 in animal models of DM1. AMO-02 is an inhibitor of GSK3ß that has demonstrated pre-clinical efficacy in transgenic models and reversal of muscle cell deficits in ex vivo tissue samples in patients with DM1.
Inhibition of increased levels of GSK3ß is known to reverse cognitive and behavioral deficits in transgenic models of syndromic autism, a developmental disorder characterized by social communication deficits and repetitive behaviors.
Jones, Timchenko, et al. 2012. J. Clin. Invest. 122(12), 4461-4472.
Jones, Timchenko et al. 2015. PNAS 112 (26), 8041-8045.
DEVELOPMENT & CLINICAL TRIAL UPDATE
AMO has initiated a phase 2 clinical study in the United Kingdom for AMO-02 for the treatment of congenital myotonic dystrophy. This phase 2 exploratory study focuses on adolescent and adult patients with congenital and juvenile onset myotonic dystrophy. This is the first sponsor-led clinical study evaluating an investigational therapy in this patient group as part of a development program. Previously AMO Pharma completed discussions with the U.S. Food and Drug Administration (FDA) an has opened an investigational new drug (IND) application for AMO-02. AMO is planning additional global studies of AMO-02 in congenital onset myotonic dystrophy. FDA has granted Fast Track and Orphan Drug Designation to this program.
More information on the Phase 2 clinical trial for AMO-02 in congenital myotonic dystrophy can be found at https://clinicaltrials.gov/ct2/show/NCT02858908.