Researchers at the University of Valencia discovered that microRNAs that repress MBNL are overexpressed in muscle biopsies of patients with DM1 and in different animal models of the disease, including the muscles of the HSALR mouse model. In experiments in the HSALR mouse, anti-miRs were shown to increase MBNL protein expression, reduce toxic DMPK foci, improve splicing defects, reduce myotonia and improve grip strength (Cerro et al. 2018).
Myotonic Dystrophy Type 1 (DM1) is a highly disabling multisystemic disease with no known cure. DM1 symptoms affect mainly the musculoskeletal, nervous, and cardiac systems, although alterations in other systems or organs have also been reported. The onset of symptoms occurs most commonly during adolescence, and affected individuals have a shortened lifespan.
ARTHEx proposes a novel therapeutic approach for the treatment of DM1. We propose to inhibit miRNAs repressing MBNL proteins to increase MBNL levels and to release sequestered MBNL from toxic DMPK foci. This dual approach has shown promise in preclinical in vitro and in vivo models of the disease.