AAV Vectors, A Step Toward Duchenne Muscular Dystrophy Clinical Trials

Posted September 18, 2018

Dongsheng Duan, Ph.D., University of Missouri

Dongsheng Duan, Ph.D., University of Missouri
Dr. Dongsheng Duan,
University of Missouri

Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the dystrophin gene, which codes for an essential muscle protein. DMD is the most common lethal muscle disease affecting 250,000 to 300,000 boys and young man worldwide. The well-defined genetic cause of DMD makes it an excellent candidate for gene therapy approaches for treatment, such as delivering mini- or micro-gene dystrophin by viral vectors, genome editing, or oligonucleotide-mediated exon skipping.

For more than 10 years much of the research on micro-gene therapy for DMD has focused on optimization of the delivery vectors, the micro-gene constructs, delivery methods and translation of this therapy to large mammals. Dr. Dongsheng Duan, with support from an Investigator Initiated Research Award, sought to engineer an AAV micro-dystrophin vector and then test the vector for body wide gene therapy in a large mammal model of DMD. The AAV used in the study is a protein shell derived from a harmless virus called adeno-associated virus. A therapeutic gene can be encapsulated in this protein shell to become a gene therapy vector. Initial experiments confirmed that an AAV vector can lead to body wide gene transfer in a dystrophic canine model. Next Dr. Duan injected his optimized AAV micro-dystrophin vector into young adult affected animals through the vein. Dr. Duan found that the optimized vector did not cause harm to dystrophic animals. Four months after a single-dose treatment, Dr. Duan found micro-dystrophin in every muscle in treated animals. When examined under a microscope, AAV micro-dystrophin treated muscle showed a much healthier look than untreated muscle. Dr. Duan has continued this promising work to determine how long therapeutic benefits can be maintained and preliminary evidence from a partially DMDRP funded study, suggests that a single dose treatment with the optimized AAV micro-dystrophin vector does result in therapeutic benefits for at least two years without adverse reactions. Dr. Duan’s efforts have provided the foundation for a collaboration with Solid Bioscience to initiate a clinical trial studying AAV micro-dystrophin gene transfer in adolescents and children with DMD (NCT03368742).


Public and Technical Abstracts: A Translational Pathway Toward a Clinical Trial Using the Second-Generation AAV Micro-Dystrophin Vector

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Last updated Thursday, May 26, 2022