Gene therapy for Duchenne muscular dystrophy

Abstract

Introduction: Duchenne muscular dystrophy (DMD) is a relatively common inherited disorder caused by defective expression of the protein dystrophin. The most direct approach to treating this disease would be to restore dystrophin production in muscle. Recent progress has greatly increased the prospects for successful gene therapy of DMD, and here we summarize the most promising developments.

Areas covered: Gene transfer using vectors derived from adeno-associated virus (AAV) has emerged as a promising method to restore dystrophin production in muscles bodywide, and represents a treatment option applicable to all DMD patients. Using information gleaned from PubMed searches of the literature, attendance at scientific conferences and results from our own lab, we provide an overview of the potential for gene therapy of DMD using AAV vectors including a summary of promising developments and issues that need to be resolved prior to large-scale therapeutic implementation.

Expert opinion: Of the many approaches being pursued to treat DMD and Becker muscular dystrophy, gene therapy based on AAV-mediated delivery of microdystrophin is the most direct and promising method to treat the cause of the disorder. The major challenges to this approach are ensuring that microdystrophin can be delivered safely and efficiently without eliciting an immune response.

Keywords:

• adeno-associated viral vectors
• Becker muscular dystrophy
• Duchenne muscular dystrophy
• dystrophin
• gene therapy
• immune response
• micro-dystrophin
• micro-utrophin
• tolerization

Declaration of interest

This work has been supported by the NIH (NIAMS) via funding grants U54 AR065139 and R01 AR44533 to JS Chamberlain. JS Chamberlain is a member of the scientific advisory board of Solid GT and Akashi Scientific. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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