Evidence map›Paper›PMID 39044305›Full record

ArticleSkeletal muscle2024

AAV-NRIP gene therapy ameliorates motor neuron degeneration and muscle atrophy in ALS model mice.

Hsin-Hsiung Chen, Hsin-Tung Yeo, Yun-Hsin Huang, Li-Kai Tsai, Hsing-Jung Lai, Yeou-Ping Tsao, Show-Li Chen

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Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

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7citing papers in PubMed, 1 pooled it
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Hsin-Hsiung ChenGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
Hsin-Tung YeoGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
Yun-Hsin HuangGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
Li-Kai TsaiDepartment of Neurology, National Taiwan University Hospital, Taipei, 100, Taiwan.
Hsing-Jung LaiDepartment of Neurology, National Taiwan University Hospital, Taipei, 100, Taiwan.
Yeou-Ping TsaoDepartment of Ophthalmology, Mackay Memorial Hospital, Taipei, 104, Taiwan.
Show-Li ChenGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan. showlic@ntu.edu.tw.

Funding

National Science and Technology Council NSTC 112-2320-B-002-004National Taiwan University 10R891903
6 · The paper itself

Abstract

backgroundAmyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration, leading to neuromuscular junction (NMJ) dismantling and severe muscle atrophy. The nuclear receptor interaction protein (NRIP) functions as a multifunctional protein. It directly interacts with calmodulin or α-actinin 2, serving as a calcium sensor for muscle contraction and maintaining sarcomere integrity. Additionally, NRIP binds with the acetylcholine receptor (AChR) for NMJ stabilization. Loss of NRIP in muscles results in progressive motor neuron degeneration with abnormal NMJ architecture, resembling ALS phenotypes. Therefore, we hypothesize that NRIP could be a therapeutic factor for ALS.

methodsWe used SOD1 G93A mice, expressing human SOD1 with the ALS-linked G93A mutation, as an ALS model. An adeno-associated virus vector encoding the human NRIP gene (AAV-NRIP) was generated and injected into the muscles of SOD1 G93A mice at 60 days of age, before disease onset. Pathological and behavioral changes were measured to evaluate the therapeutic effects of AAV-NRIP on the disease progression of SOD1 G93A mice.

resultsSOD1 G93A mice exhibited lower NRIP expression than wild-type mice in both the spinal cord and skeletal muscle tissues. Forced NRIP expression through AAV-NRIP intramuscular injection was observed in skeletal muscles and retrogradely transduced into the spinal cord. AAV-NRIP gene therapy enhanced movement distance and rearing frequencies in SOD1 G93A mice. Moreover, AAV-NRIP increased myofiber size and slow myosin expression, ameliorated NMJ degeneration and axon terminal denervation at NMJ, and increased the number of α-motor neurons (α-MNs) and compound muscle action potential (CMAP) in SOD1 G93A mice.

conclusionsAAV-NRIP gene therapy ameliorates muscle atrophy, motor neuron degeneration, and axon terminal denervation at NMJ, leading to increased NMJ transmission and improved motor functions in SOD1 G93A mice. Collectively, AAV-NRIP could be a potential therapeutic drug for ALS.

Indexed as

Amyotrophic Lateral SclerosisDependovirusDisease Models, AnimalGenetic TherapyMice, TransgenicMotor NeuronsMuscular AtrophyAnimalsGenetic VectorsHumansMaleMiceMuscle, SkeletalNerve DegenerationNeuromuscular JunctionSuperoxide Dismutase-1Superoxide Dismutase-1AAVALSGene therapyMotor neuronMuscleNeuromuscular junctionNRIPSOD1 G93A

Identifiers

PMID39044305
PMCPMC11267858

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.