Key result
Systemic delivery of AAV2/9 CMV Large1 in >34-week-old myd mice with advanced muscular dystrophy restored muscle function and greatly improved survival.
Why the study?
It is unclear whether gene editing or gene transfer can restore muscle function and improve survival in the late stages of muscular dystrophy.
Does systemic delivery of AAV Large1 improve survival and muscle function in >34-week-old myd mice with advanced muscular dystrophy?
Does systemic delivery of AAV Large1 improve survival and muscle function in >34-week-old myd mice with advanced muscular dystrophy?
Systemic gene transfer of Large1 can restore muscle function and greatly improve survival even in late stages of severe muscular dystrophy in a mouse model.
This is the authors' abstract. We don't add key points for this paper.
Muscular dystrophy is a progressive and ultimately lethal neuromuscular disease. Although gene editing and gene transfer hold great promise as therapies when administered before the onset of severe clinical symptoms, it is unclear whether these strategies can restore muscle function and improve survival in the late stages of muscular dystrophy. Large myd /Large myd ( myd ) mice lack expression of like-acetylglucosaminyltransferase-1 ( Large1 ) and exhibit severe muscle pathophysiology, impaired mobility, and a markedly reduced life span. Here, we show that systemic delivery of AAV2/9 CMV Large1 (AAV Large1 ) in >34-week-old myd mice with advanced disease restores matriglycan expression on dystroglycan, attenuates skeletal muscle pathophysiology, improves motor and respiratory function, and normalizes systemic metabolism, which collectively and markedly extends survival. Our results in a mouse model of muscular dystrophy demonstrate that skeletal muscle function can be restored, illustrating its remarkable plasticity, and that survival can be greatly improved even after the onset of severe muscle pathophysiology.
Late-stage AAV-Large1 gene transfer restores function and extends survival in myd mice; leaves open translation to advanced human muscular dystrophy.
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Yonekawa et al. (2022) studied Muscular dystrophy. AAV2/9 CMV Large1 (AAV Large1) was evaluated on Muscle function and survival. Systemic delivery of AAV2/9 CMV Large1 in >34-week-old myd mice with advanced muscular dystrophy restored muscle function and greatly improved survival.
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