First Report of Systemic Delivery of Micro-dystrophin Gene Therapy in Children With Duchenne Muscular Dystrophy

Jerry Mendell, MD

Jerry Mendell, MD, neurologist and principal investigator with the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children’s Hospital

One-year data from the first four patients to receive a single dose of the rAAVrh74.MHCK7.microdystrophin gene therapy is published in JAMA Neurology.

US News Badge Neurology and NeurosurgeryUS News Badge Honor RollResearchers from Nationwide Children’s Hospital have published results in JAMA Neurology from the first four children with Duchenne muscular dystrophy (DMD) treated in the first clinical trial of systemic delivery of micro-dystrophin gene therapy in children. Initial findings suggest that the therapy can provide functional improvement that is greater than that observed under the standard of care.

DMD is a fatal neuromuscular disease that occurs in approximately one in every 5,000 males worldwide and is caused by a mutation in the gene that encodes for dystrophin. The dystrophin
gene itself is too large to fit into the adeno-associated viral vector used in the gene therapy technology utilized by the study. Researchers have developed micro-dystrophin as a microgene that provides function while still fitting in the vector.

“Duchenne muscular dystrophy is difficult to treat, and gene therapy offers a needed option having the potential to alter the course of the disease,” says Jerry Mendell, MD, the study’s co-author and principal investigator with the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children’s.


Four ambulatory participants, aged 4 to 7 years at time of infusion, were treated with a single dose of 2.0 x 1014 vg/kg rAAVrh74.MHCK7.micro-dystrophin (SRP-9001 micro-dystrophin, Sarepta Therapeutics), which was infused through a peripheral limb vein. All treatment-related events were mild to moderate and there were no serious adverse events.

“We are very pleased to report successful delivery of the micro-dystrophin transgene to the nuclei – corresponding to robust gene expression and proper localization of micro-dystrophin. This coincides with improvements in functional measurements in all study participants who received SRP-9001,” Dr. Mendell says.

Participants had confirmed vector transduction and showed functional improvement of North Star Ambulatory Assessment (NSAA) scores. The NSAA is a 17-item measure of ambulatory functions with a score range from 0 to 34.

“The publication of these results further supports the potential for SRP-9001 to provide clinically meaningful functional improvements in terms of speed and magnitude for DMD patients,” says Louise Rodino-Klapac, PhD, senior vice president of gene therapy at Sarepta Therapeutics. “We look forward to advancing our ultimate goal of profoundly improving the lives of as many patients living with DMD as possible.”

Sarepta has exclusive rights to the gene therapy program initially developed at AWRI at Nationwide Children’s.

Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, Iammarino MA, Alfano LN, Nicholl A, Al-Zaidy S, Lewis S, Church K, Shell R, Cripe LH, Potter RA, Griffin DA, Pozsgai E, Dugar A, Hogan M, Rodino-Klapac LR. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin  in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurology. 2020 Jun 15;77(9):1–10.

A Decade of Remarkable Transformation: Neurology

During the past decade Neurology faculty have developed many groundbreaking clinical programs and led scientific discoveries for previously fatal diseases. The faculty increased by more than 70% to the current staff of 33 neurologists and for the past four consecutive years, U.S. News & World Report has ranked Nationwide Children’s in the top seven for Neurology and Neurosurgery.

  • 2010: Named Batten Disease Center of Excellence by BDSRA
  • 2010: First Intracranial Hypertension Program for Pediatric Patients
  • 2012: First Dedicated Program for Infantile Spasms
  • 2014: Columbus and Nationwide Children's Host Child Neurology Society Annual Meeting
  • 2017: Dr. Jerry Mendell and Team Publish SMA-1 Gene Therapy Results in NEJM; Paves Way for FDA’s 2019 Approval
  • 2019: Named CMT Center of Excellence by Charcot-Marie Tooth Association
  • 2020: Results of First Successful Gene Therapy for DMD Led by Dr. Mendell and Team Published in JAMA Neurology

A Decade of Remarkable Transformation: Neurosurgery

From the recruitment of highly skilled neurosurgeons with diverse experience to the launch of a pediatric neurosurgery fellowship the past decade has seen exceptional growth for Neurosurgery. The program has risen to national prominence, recognized in the top seven by U.S. News & World Report for four consecutive years.

  • 2010: New Neurosurgical OR Equipped with iMRI and Stereotactic Guidance
  • 2014: Jeffrey Leonard, MD, Named Neurosurgery Chief
  • 2015: Selective Dorsal Rhizotomy Program Helps Children with Spasticity from Across U.S.
  • 2016: Joined Hydrocephalus Clinical Research Network (HCRN) as 1 of only 13 Sites in North America
  • 2017: Among First in U.S. to Provide Responsive Neurostimulation Therapy for Children With Intractable Epilepsy
  • 2019: New Craniofacial Disorders Center Provides Multidisciplinary Care for Craniosynostosis
  • 2020: Ranked in Top 7 by U.S. News & World Report 4th Consecutive Year