Therapy for Muscular Dystrophy by Inhibition of Mechanosensitive Ion Channels

Dr Sachs
Rose Pharmaceuticals, USA

Saturday 15th January 2011

Rose Pharmaceuticals proposed GsMTx4 as a peptide therapeutic to reduce the activity of stretch activated ion channels. GsMTx4 has been shown in vitro to decrease Ca2+ uptake associated with eccentric contractions and activation of calpains in dystrophic muscle fibers and hence is likely to reduce the severity of long term muscle damage. Since GsMTx4 has a different target than any other pharmaceutical in development, it could potentially be combined in a drug cocktail with other agents. TACT’s assessment concluded that the development of GsMTx4 is still at an early stage. Although in vitro data show a good safety profile, TACT considered it important that an initial safety screen be conducted in vivo to determine the risk of cardiac arrhythmia as a consequence of possible action on hERG receptors before committing to further development. Assuming an acceptable safety profile, TACT determined it critical to establish an in vivo therapeutic window that changes the disease in animal models of muscular dystrophy, particularly with respect to the ability to reduce damage associated with abnormal activity of the mechanosensitive ion channels, prior to additional pre-clinical pharmacology testing, and Regulatory activities to support a clinical trial application. If the studies above support further development, TACT recommended engaging clinical researchers with expertise in the disease early in the process to help identify the most suitable patient population for initial clinical testing.

12 Apr 2017