Galectin 1: A novel small protein therapy for Duchenne muscular dystrophy

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DESCRIPTION (provided by applicant): Duchenne Muscular Dystrophy (DMD) is a fatal muscle disease affecting 1 in every 3500 male births. DMD results from mutations in the gene encoding the dystrophin, a 427 kDa scaffolding protein responsible for providing a mechanical link between the muscle fiber actin cytoskeleton and a transmembrane protein complex called the dystrophin-associated glycoprotein complex (DGC). Although life expectancy for DMD patients has gone up in recent years, the only currently approved treatment remains corticosteroids, which have limited positive effects including inflammation inhibition and counterproductive side effects. Recent research studies have focused on using virally mediated gene replacement, direct gene repair, myoblast cell transfer, small molecule protein enhancement, exon skipping small molecules, and protein therapeutics. The Burkin lab has recently shown that recombinant mouse Galectin-1 is capable of stabilizing and restoring the normal protein levels of dystrophin-associated proteins normally in DMD. Galectin-1 treatment also leads to elevated levels of both utrophin and ?7?1 integrin in skeletal muscle, critical modifying proteins that act to protect the fragile sarcolemmal from damage in the absence of dystrophin. The enhanced sarcolemmal stability leads to a decreased myofiber regeneration and damage. Galectin-1 also functions in muscle to limit inflammation and thereby fibrosis. Finally, Galectin-1 treated mdx mice displayed elevated strength and activity levels relative to controls. Strykagen plans to further develop Galectin-1 protein therapy towards an IND application by producing purified human Galectin-1 protein capable of getting FDA approval for phase I clinical trials. In collaboration with our academic partner the purified recombinant galectin-1 will be used in preclinical studies in the mdx mice to demonstrate muscle protecting properties. Results from this study should lead directly into a phase II STTR grant for preclinical studies in the GRMD dog model of DMD. Together these studies will lead to an IND application with the FDA and clinical trials to develop Galectin-1 protein as a novel treatment for DMD.