Abstract:
: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 dy w /dy w 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 dy w /dy w mice offers profound therapeutic effects in both skeletal muscle and nervous system.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Qiao C,Dai Y,Nikolova VD,Jin Q,Li J,Xiao B,Li J,Moy SS,Xiao Xdoi
10.1016/j.omtm.2018.01.005subject
Has Abstractpub_date
2018-01-31 00:00:00pages
47-56issn
2329-0501pii
S2329-0501(18)30006-8journal_volume
9pub_type
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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