FDA approves first gene therapy for treating Duchenne muscular dystrophy
Delandistrogene moxeparvovec was approved by the Food and Drug Administration (FDA) in June 2023 for the treatment of ambulatory patients ages 4-5 years with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the DMD gene and do not have a pre-existing medical reason preventing treatment with the therapy. Approval was granted via the accelerated approval pathway.
Delandistrogene moxeparvovec is a recombinant adeno-associated virus vector-based gene therapy designed to deliver a gene that leads to expression of a microdystrophin comprising key functional domains of the normal dystrophin protein. It is administered as a single intravenous dose.
The approval was based on analysis of results submitted to the FDA from randomized trials indicating that the microdystrophin was expressed in patients treated with the therapy. A clinically meaningful and statistically significant difference in North Star Ambulatory Assessment score was reported for patients treated with delandistrogene moxeparvovec compared with a propensity-score-weighted external control cohort after 1 year.[74] Adverse effects noted in the trials included myocarditis, elevations of troponin-I, acute liver injury, and thrombocytopenia. Studies are ongoing to demonstrate clinical benefit.
Summary
Definition
History and exam
Key diagnostic factors
- family history of DMD
- male sex
- imbalance of lower limb strength
- lower extremity musculotendinous contractures
- delayed motor milestones
- calf hypertrophy
- ambulation difficulty and falls
- diminished muscle tone and deep tendon reflexes
- normal sensation
- Gowers sign
Other diagnostic factors
- toe walking
- hypotonia
- hyperactivity
- urinary and bowel incontinence
- mild to severe intellectual disability
Risk factors
- family history
- male sex
Diagnostic investigations
1st investigations to order
- serum creatine kinase (CK)
- genetic testing
Investigations to consider
- electromyogram (EMG)
- muscle biopsy
- muscle MRI
Treatment algorithm
DMD: ambulatory stage
DMD: early nonambulatory stage
DMD: late nonambulatory stage
spinal muscular atrophy (SMA)
Contributors
Authors
Pinki Munot, MD
Consultant Paediatric Neurologist
Great Ormond Street Hospital for Children
London
UK
Disclosures
PM is a principal investigator for the Sideros trial in DMD and the ARGNX trial in Myasthenia, and a sub-investigator for the SHINE trial. PM was reimbursed for presenting at the PULSE 65 rare disease day for GPs in December 2023 and for the RCPCH 2022 lunch time symposium by PTC therapeutics.
Acknowledgements
Dr Pinki Munot would like to gratefully acknowledge Dr John R. Bach, Dr Aravindhan Veerapandiyan, and Dr Bilal Saulat, previous contributors to this topic.
Disclosures
JRB, AV, and BS declare that they have no competing interests.
Peer reviewers
Lisa D. Hobson-Webb, MD
Assistant Professor of Medicine
Department of Medicine/Neurology
Duke University Medical Center
Durham
NC
Disclosures
LDH-W declares that she has no competing interests.
Martin K. Childers, DO, PhD
Associate Professor Neurology and Regenerative Medicine
Wake Forest University Health Sciences
Winston-Salem
NC
Disclosures
MKC declares that he has no competing interests.
Adnan Manzur, FRCPCH
Consultant Paediatric Neurologist
Great Ormond Street Hospital for Children NHS Trust
London
UK
Disclosures
AM has been paid an honorarium for giving lectures at the Imperial College Educative Training Courses for GPs and post-graduate doctors. AM is the lead author of the Cochrane review of corticosteroids in Duchenne muscular dystrophy. He is also the Lead Clinician of the NorthStar Clinical Network for Management of Neuromuscular Disorders in the UK.
Richard W. Orrell, BSc, MD, FRCP
Senior Lecturer and Consultant Neurologist
Department of Clinical Neuroscience
UCL Institute of Neurology
London
UK
Disclosures
RWO is an author of a reference cited in this topic.
Differentials
- Polymyositis
- Static encephalopathies (cerebral palsy)
More DifferentialsGuidelines
- Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management
- Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management
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