遗传增强
肌营养不良
疾病
基因表达
肌肉组织
基因
病毒载体
医学
生物
内科学
生物信息学
内分泌学
遗传学
重组DNA
作者
Patricia Lam,Deborah A. Zygmunt,Anna Ashbrook,Macey Bennett,Tatyana A. Vetter,Paul T. Martin
标识
DOI:10.1016/j.ymthe.2024.06.028
摘要
Recent clinical studies of single gene replacement therapy for neuromuscular disorders have shown they can slow or stop disease progression, but such therapies have had little impact on reversing muscle disease that was already present. In order to reverse disease in patients with muscular dystrophy, new muscle mass and strength must be rebuilt at the same time that gene replacement prevents subsequent disease. Here, we show that treatment of FKRPP448L mice with a dual FKRP/FST gene therapy packaged into a single AAV vector can build muscle strength and mass that exceed levels found in wild-type mice and can induce normal ambulation endurance in a one-hour walk test. Dual FKRP/FST therapy also showed more even increases in muscle mass and amplified muscle expression of both genes relative to either single gene therapy alone. These data suggest that treatment with a single AAV bearing dual FKRP/FST gene therapies can overcome loss of ambulation by improving muscle strength at the same time it prevents subsequent muscle damage. This design platform could be used to create therapies for other forms of muscular dystrophy that may improve patient outcomes.
科研通智能强力驱动
Strongly Powered by AbleSci AI