Neuromuscular Disorders Research

Jerry R. Mendell, MD, Director of the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, is an international leader in the development of innovative treatments for neuromuscular diseases. A primary focus of the Center for Gene Therapy is curing muscular dystrophies and Nationwide Children’s Hospital has been part of the Muscular Dystrophy Association’s Clinical Research Network since 2008. Investigators are currently focused on developing treatments for:

• Amyotrophic lateral sclerosis (ALS)
• Becker muscular dystrophy
• Charcot-Marie-Tooth Neuropathy
• Duchenne muscular dystrophy
• Fasioscapulohumeral muscular dystrophy
• Inclusion body myositis
• Limb girdle muscular dystrophy type 2D (alpha sarcoglycanopathy)
• Spinal muscular atrophy

Learn about Heart Research in Neuromuscular Disease, Duchenne Muscular Dystrophy Research and Spinal Muscular Atrophy Research.

Neuromuscular Disorders Research Faculty

Louis Chicoine, MD
K. Reed Clark, PhD
Kevin Flanigan, MD
Haiyan Fu, PhD
Scott Harper, PhD
Brian K. Kaspar, PhD
Paul T. Martin, PhD
Douglas M. McCarty, PhD
Jerry R. Mendell, MD
Federica Montanaro, PhD
Louise Rodino-Klapac, PhD
Zarife Sahenk, MD, PhD

Latest Findings in Neuromuscular Disorders Research

New Model for Understanding Nonsense Mutation-Associated Becker Muscular Dystrophy

This study presents a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of Becker muscular dystrophy nonsense mutations with a subset of Duchenne muscular dystrophy exons prone to mutation-induced exon skipping.

Access an abstract of this study: Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Hum Mutat. 2011 Mar;32(3):299-308.

Knee Extensor Strength Exhibits Potential to Predict Function in Sporadic Inclusion-Body Myositis

This study addressed the challenging issue of potential use of muscle strength to predict function in clinical trials. Quadriceps (knee extensor) strength correlated with performance in this large cohort of sIBM subjects, which demonstrated its potential to predict function in this disease. These data provide initial support for use of muscle strength as a surrogate for function, although validation in a clinical trial is required.

Access an abstract of this study: Knee extensor strength exhibits potential to predict function in sporadic inclusion-body myositis. Muscle Nerve. 2012 Feb;45(2):163-8. doi: 10.1002/mus.22321.

Childhood Onset of Limb-Girdle Muscular Dystrophy

Limb-girdle muscular dystrophies comprise a rare heterogeneous group of genetic muscular dystrophies.  A definitive diagnosis among various subtypes is challenging, and the data presented here provide neuromuscular clinicians with additional information to help attain that goal.

Access an abstract of this study: Childhood onset of limb-girdle muscular dystrophy. Pediatr Neurol. 2012 Jan;46(1):13-23.

Muscle Induced to Regenerate May Support Tumor Development

Investigators previously reported that mice with muscular dystrophy develop embryonal rhabdomyosarcoma (eRMS) with a low incidence after 1 year of age and that almost all such tumors contain cancer-associated p53 mutations. These studies further suggest that consideration should be given to the potential of the muscle microenvironment to support tumor development in regenerative therapies for myopathies.

Access an abstract of this study: Induction of a regenerative microenvironment in skeletal muscle is sufficient to induce embryonal rhabdomyosarcoma in p53-deficient mice. J Pathol. 2012 Jan;226(1):40-9. doi: 10.1002/path.2996.

Becker Muscular Dystrophy Due to an Inversion of Exons 23 and 24 of the DMD Gene

This report describes a case of Becker muscular dystrophy caused by an inversion of exons 23 and 24 of the Duchenne muscular dystrophy gene.  The results demonstrate the limits of sensitivity and specificity of current tests and highlight the need for more detailed analysis when intronic deletions are detected by comparative genome hybridization methods.

Access an abstract of this study: Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene. Muscle Nerve. 2011 Nov;44(5):822-5. doi: 10.1002/mus.22226.

Cardiovascular Magnetic Resonance of Cardiomyopathy in Limb Girdle Muscular Dystrophy 2B and 2I

In this study of patients with these two forms of limb girdle muscular dystrophy, cardiovascular magnetic resonance (CMR) was used to more specifically define markers of cardiomyopathy including systolic dysfunction, myocardial fibrosis, and diastolic dysfunction.

Access an abstract of this study: Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I. J Cardiovasc Magn Reson. 2011 Aug 4;13:39.

Current Neuromuscular Disorders Research Grants

Glycosyltransferase Therapy for Myopathies, National Institutes of Health (Paul Martin)

Translational Research in the Dystrophinopathies, National Institutes of Health (Kevin Flanigan)

Translational Research in the Dystrophinopathies, National Institutes of Health (Kevin Flanigan)

Unique cardiac interactions of dystrophin and their role in dilated cardiomyopathy, American Heart Association of Ohio (Eric Johnson)

AAV9 Gene Therapy for treating Mucopolysaccharidosis IIIB by systemic vector delivery, Ben’s Dream-Sanfilippo Research Foundation (Haiyan Fu)

Role of Potent Trophic Factors on Glia and Motor Neurons in ALS, National Institutes of Health (Brian Kaspar)

The Heart in Duchenne Muscular Dystrophy, Muscular Dystrophy Association, Inc (Kevin Flanigan)

Delivery of Therapeutic Genes in Motor Neuron Disease, Ohio State University Research Foundation, National Institutes of Health, National Institute of Neurological Disorders and Stroke (Brian K. Kaspar)

Vascular Delivery of alpha-Sarcoglycan for Limb Girdle Muscular Dystrophy 2D, National Institutes of Health (Jerry Mendell)

NT-3 Gene Therapy to Improve Peripheral Nerve Function Induced by Genetic Defect, National Institutes of Health (Zarife Sahenk)

Targeting Astrocytes as a Therapy for ALS: Testing the Effectiveness of AAV9 as a Therapeutic Vector for Gene Delivery across the Blood Brain Barrier, Robert Packard Center for ALS Research at Johns Hopkins (Brian Kaspar)

“This Month in Muscular Dystrophy” Podcast

Listen to both current and previous editions of the Muscular Dystrophy Podcast.

• Gene Transfer of Follistatin: Dr. Mendell Discusses Implications for Muscle Disease
• Prof. Kate Bushby Discusses Clinical Care Standards in Muscular Dystrophy
• Dr. Federica Montanaro Discusses Cardiomyopathy in Becker Muscular Dystrophy
• Dr. Annemieke Aartsma-Rus Discusses Progress in Antisense Oligonucleotide Therapies
• Dr. Scott Harper Discusses DUX4 as a Potential Candidate Gene for Facioscapulohumeral Muscular Dystrophy

Of Note

Nationwide Children’s Hospital Researchers Receive Neurology Award for Contribution to Clinical Neuroscience
Jerry Mendell, MD, director of the Center for Gene Therapy in The Research Institute at Nationwide Children’s Hospital, and his fellow researchers, are the latest recipients of the Annals of Neurology prize for an outstanding contribution to clinical neuroscience. Read more>