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Cited by 23Virus-based gene therapy researchNeurogenetic and Muscular Disorders ResearchMuscle Physiology and Disorders

Amelioration of Muscle and Nerve Pathology in LAMA2 Muscular Dystrophy by AAV9-Mini-Agrin

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Qiao, Chunping, Dai, Yi, Nikolova, Viktoriya D., Jin, Quan, Li, Jianbin, Xiao, Bin, Li, Juan, Moy, Sheryl S. +1 more·2018·Molecular Therapy - Methods & Clinical Development
DOI 10.1016/j.omtm.2018.01.005PMC PMC5948311
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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.

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  • More recently, the same group upgraded to the AAV9 serotype and showed that AAV9mini-agrin vectors additionally ameliorated peripheral neuropathy and cognition, thus offering superior therapeutic effects compared to the AAV1 serotype.

    “More recently, the same group upgraded to the AAV9 serotype and showed that AAV9mini-agrin vectors additionally ameliorated peripheral neuropathy and cognition, thus offering superior therapeutic effects compared to the AAV1 serotype [117].”

    From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [117]

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Sorted by citations

Authors
Qiao, C., Dai, Y., Nikolova, V. D., Jin, Q., Li, J., Xiao, B., Li, J., Moy, S. S., & Xiao, X.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Xiao, Xiao
ORCID
Venue
Molecular Therapy - Methods & Clinical Development
Publisher
Elsevier BV
Published
2018-06
Volume
9
Pages
47-56
ISSN
2329-0501 (ISSN-L)
DOI
10.1016/j.omtm.2018.01.005
PMC
PMC5948311
OpenAlex
W2788030505
Cited by
23
References
4
Citations by year
2026: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 3
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NICHD (U54HD079124)
  • NIH/NINDS (1RO1 NS079568)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
LAMA2-related muscular dystrophy, laminin alpha 2, AAV9 vector, gene replacement therapy, congenital muscular dystrophy, peripheral nerve pathology, myelination, basement membrane, motor function, skeletal muscle pathology, lifespan extension

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