title: Galectin-1 Protein Therapy Prevents Pathology and Improves Muscle Function in the mdx Mouse Model of Duchenne Muscular Dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by mutations in the dystrophin gene, leading to the loss of a critical component of the sarcolemmal dystrophin glycoprotein complex. Galectin-1 is a small 14 kDa protein normally found in skeletal muscle and has been shown to be a modifier of immune response, muscle repair, and apoptosis. Galectin-1 levels are elevated in the muscle of mouse and dog models of DMD. Together, these findings led us to hypothesize that Galectin-1 may serve as a modifier of disease progression in DMD. To test this hypothesis, recombinant mouse Galectin-1 was produced and used to treat myogenic cells and the mdx mouse model of DMD. Here we show that intramuscular and intraperitoneal injections of Galectin-1 into mdx mice prevented pathology and improved muscle function in skeletal muscle. These improvements were a result of enhanced sarcolemmal stability mediated by elevated utrophin and α7β1 integrin protein levels. Together our results demonstrate for the first time that Galectin-1 may serve as an exciting new protein therapeutic for the treatment of DMD.
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA.
authors.forename: Pam M
authors.initials: PM
authors.lastname: Van Ry
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Wuebbles
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Key
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA. Electronic address: dburkin@medicine.nevada.edu.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Burkin
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D037483:Galectin 1 / Q000627:therapeutic use*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012508:Sarcolemma / Q000378:metabolism; D049411:Utrophin / Q000378:metabolism
chemical_list: D037483:Galectin 1; D016023:Integrins; C445499:LGALS1 protein, human; D011994:Recombinant Proteins; D049411:Utrophin; D049030:Dystroglycans; C082908:integrin alpha7beta1