Galectin-1 Protein Therapy for Congenital Muscular Dystrophy

Abstract Lamininrelated congenital muscular dystrophyLAMACMDalso known as Merosin Deficient Congenital Muscular DystrophyMDC Ais a fatal muscle wasting disease that affects patients from birthLAMACMD results from mutations in the LAMAgene resulting in loss of lamininproteinLamininis required for the formation of the heterotrimers lamininand lamininwhich are major constituents of the skeletal and cardiac muscle basal laminaLAMACMD patients exhibit severe muscle weakness from birthare confined to a wheelchairrequire ventilator assistance to breathe and have reduced life expectancyThere is currently no effective treatment or cure for LAMACMD and all affected children will die from this genetic diseaseGalectinis akDa protein localized in the myomatrix that interacts with laminin andintegrin and has been shown to stabilize dystrophic muscleThe Burkin lab has recently shown that treatment with recombinant human Galectinprotein leads to elevated levels ofintegrin in the skeletal muscle of the dyW mouse model of LAMACMDGalectintreatment increased the capacity for muscle repair and functioned to limit muscle inflammation and fibrosisGalectincould interact with other laminin isoforms that are up regulated in LAMACMD to stabilize their interaction with muscleWhat is unclear from these studies is the mechanism of actionthe optimal dosing and pharmacokinetic and pharmacodynamicPK PDand toxicology profile of exogenously delivered Galectinto prevent disease progression in laminindeficient muscleIn the proposal Strykagen will optimize Galectindosingdefine the PK PD profiletoxicology and determine the effectiveness of optimized Galectinprotein treatment on disease progression in a mouse model of LAMACMDTogether these studies will contribute to an IND application to develop recombinant human Galectinprotein as a novel treatment for patients with LAMACMD Project Narrative Laminincongenital muscular dystrophyLAMACMDis a fatal muscle disease that currently has no cure or treatment optionsDrDean Burkin has identified that Galectina smallkDa proteinincreasesintegrin to therapeutic levels in the dyW mouse model of LAMACMDThis study aims to optimize the dosingPK PD and toxicology of recombinant human galectinprotein in a mouse model of LAMACMD and examine onand off target drug activity in mouse muscle and using patient myogenic cells