Laminin-111 protein therapy after disease onset slows muscle disease in a mouse model of laminin-α2 related congenital muscular dystrophy
| Autor: | Ariany Oliveira-Santos, Brandon W Conner, Dean J. Burkin, Pamela Barraza-Flores, Katherine E. Bukovec, Robert W. Grange, Marisela Dagda |
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| Rok vydání: | 2020 |
| Předmět: |
Bioinformatics
Basement Membrane Muscular Dystrophies Laminin 111 Muscle hypertrophy Mice 03 medical and health sciences 0302 clinical medicine Protein replacement therapy Muscular Diseases Laminin Genetics medicine Animals Humans Muscle Skeletal Myopathy Molecular Biology Genetics (clinical) 030304 developmental biology 0303 health sciences biology General Medicine Muscle stiffness medicine.disease Hypotonia Disease Models Animal Mutation Congenital muscular dystrophy biology.protein General Article medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Hum Mol Genet |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddaa104 |
| Popis: | Laminin-α2 related congenital muscular dystrophy (LAMA2-CMD) is a fatal muscle disease caused by mutations in the LAMA2 gene. Laminin-α2 is critical for the formation of laminin-211 and -221 heterotrimers in the muscle basal lamina. LAMA2-CMD patients exhibit hypotonia from birth and progressive muscle loss that results in developmental delay, confinement to a wheelchair, respiratory insufficiency and premature death. There is currently no cure or effective treatment for LAMA2-CMD. Several studies have shown laminin-111 can serve as an effective protein-replacement therapy for LAMA2-CMD. Studies have demonstrated early treatment with laminin-111 protein results in an increase in life expectancy and improvements in muscle pathology and function. Since LAMA2-CMD patients are often diagnosed after advanced disease, it is unclear if laminin-111 protein therapy at an advanced stage of the disease can have beneficial outcomes. In this study, we tested the efficacy of laminin-111 protein therapy after disease onset in a mouse model of LAMA2-CMD. Our results showed laminin-111 treatment after muscle disease onset increased life expectancy, promoted muscle growth and increased muscle stiffness. Together these studies indicate laminin-111 protein therapy either early or late in the disease process could serve as an effective protein replacement therapy for LAMA2-CMD. |
| Databáze: | OpenAIRE |
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