Amelioration of Muscle and Nerve Pathology in LAMA2 Muscular Dystrophy by AAV9-Mini-Agrin
| العنوان: | Amelioration of Muscle and Nerve Pathology in LAMA2 Muscular Dystrophy by AAV9-Mini-Agrin |
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| المؤلفون: | Sheryl S. Moy, Juan Li, Chunping Qiao, Jianbin Li, Bin Xiao, Viktoriya D. Nikolova, Xiao Xiao, Quan Jin, Yi Dai |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 9, Iss, Pp 47-56 (2018) Molecular Therapy. Methods & Clinical Development |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | muscular dystrophy, 0301 basic medicine, Nervous system, Pathology, medicine.medical_specialty, lcsh:QH426-470, Genetic enhancement, Article, 03 medical and health sciences, Transduction (genetics), 0302 clinical medicine, CMD, Heterotrimeric G protein, mini-agrin, Genetics, Medicine, LAMA2, lcsh:QH573-671, Muscular dystrophy, Molecular Biology, Basement membrane, Agrin, lcsh:Cytology, business.industry, Skeletal muscle, AAV, medicine.disease, gene therapy, 3. Good health, lcsh:Genetics, 030104 developmental biology, medicine.anatomical_structure, nervous system, Molecular Medicine, business, 030217 neurology & neurosurgery |
| الوصف: | LAMA2-related muscular dystrophy (LAMA2 MD) is the most common and fatal form of early-onset congenital muscular dystrophies. Due to the large size of the laminin α2 cDNA and heterotrimeric structure of the protein, it is challenging to develop a gene-replacement therapy. Our group has developed a novel adeno-associated viral (AAV) vector carrying the mini-agrin, which is a non-homologous functional substitute for the mutated laminin α2. A significant therapeutic effect in skeletal muscle was observed in our previous study using AAV serotype 1 (AAV1). In this investigation, we examined AAV9 vector, which has more widespread transduction than AAV1, to determine if the therapeutic effects could be further improved. As expected, AAV9-mini-agrin treatment offered enhanced therapeutic effects over the previously used AAV1-mini-agrin in extending mouse lifespan and improvement of muscle pathology. Additionally, overexpression of mini-agrin in peripheral nerves of dyw/dyw mice partially amended nerve pathology as evidenced by improved motor function and sensorimotor processing, partial restoration of myelination, partial restoration of basement membrane via EM examination, as well as decreased regeneration of Schwann cells. In conclusion, our studies indicate that overexpression of mini-agrin into dyw/dyw mice offers profound therapeutic effects in both skeletal muscle and nervous system. Keywords: LAMA2, mini-agrin, muscular dystrophy, CMD, AAV, gene therapy |
| تدمد: | 2329-0501 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac71492d5dff92a331e39cb0e7d3d7aeTest https://doi.org/10.1016/j.omtm.2018.01.005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ac71492d5dff92a331e39cb0e7d3d7ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23290501 |
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