Research Initiatives

Clinical Research:

The Center for Genetic Muscle Disorders conducts innovative research in neuromuscular disorders affecting children and adults. We interact closely with other clinical researchers and basic scientists to understand disease mechanisms so as to ultimately provide novel treatments. While the genetic basis is known for most genetic muscle disorders, there are no cures and patients have few treatment options. Active participation in research programs allows the Center to better serve patients by providing direct access to potential trials for which they may be eligible.

Genetic Modifiers of Conduction Disease Risk in Myotonic Dystrophy

Johns Hopkins IRB Protocol Number: NA_00048833
Principal Investigator: Saman Nazarian, MD;
Co-Principal Investigator: Kathryn Wagner: MD, PhD

This multi-center case controlled observational study is established to determine if genetic variants that are known to modulate cardiac conduction and arrhythmia risk in the general population are associated with risk of ECG abnormalities in myotonic dystrophy. Patients with type I myotonic dystrophy with or without electrocardiographic abnormalities will be recruited. Blood samples will be collected for focused genetic analysis.

Biomarkers of Facioscapulohumeral Muscular Dystrophy (FSHD)

Johns Hopkins IRB Protocol Number: NA_00019985
Principal Investigator: Kathryn Wagner MD, PhD

This NIH-funded study is established to identify biomarkers for facioscapulohumeral muscular dystrophy (FSHD). FSHD patients and their unaffected first degree relative will undergo open muscle biopsy performed at the Johns Hopkins Outpatient Surgery Center under local anesthesia. Blood samples will be drawn from each subject to establish DNA and lymphhocyte repositories, as well as for FSHD A/B allele genotyping. De-identified muscle and blood samples will be sent to the Senator Paul D. Wellstone FSHD Muscular Dystrophy Cooperative Research Center for storage, processing and distribution to multiple institutions involved in FSHD research. The biomaterials obtained at Kennedy Krieger are studied in multiple labs and are anticipated to significantly improve the molecular understanding of this enigmatic disease. Travel funds are available. View Research Study Flyer.

Duchenne Muscular Dystrophy: Double-Blind Randomized Trial to Find The Optimum Steroid Regimen (FOR-DMD)

Johns Hopkins IRB Protocol Number: NA_00077118
Principal Investigator: Kathryn Wagner, MD, PhD

This Phase III multi-center, double-blind, parallel group, 36-60 month study funded by the NIH will compare three corticosteroid regimens in wide use in DMD: 1)daily prednisone (0.75 mg/kg/day); 2) intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off); and 3) daily deflazacort (0.9 mg/kg/day). The randomized controlled trial will address the pragmatic hypothesis that daily corticosteroids (prednisone or deflazacort) will be of greater benefit in terms of function and subject/parent satisfaction than intermittent corticosteroids (prednisone). Male participants must be >4 - <8 years of age of age with a genetically confirmed diagnosis of DMD and have never taken oral steroids. Participants will receive study medication for a minimum of three years and a maximum of five years (depending on how early the participant was recruited into the study). Participation involves visits to the study hospital every three months for the first 6 months and every six months thereafter.

View Research Study Flyer.

Related Link:

An Exploratory Study to Assess Two Doses of GSK2402968 in the Treatment of Ambulant Boys with Duchenne Muscular Dystrophy

Johns Hopkins IRB Protocol Number: NA_00051932
Principal Investigator: Kathryn Wagner, MD, PhD

This study, sponsored by GlaxoSmithKline (GSK), is a multi-center, Phase II, double-blind, placebo-controlled trial in ambulant males with DMD resulting from a mutation that can be corrected by exon skipping induced by oligomer GSK2402968. The study is designed to explore the efficacy and safety of two doses of GSK2402968 (6 mg/kg/week and 3 mg/kg/week). Based on pharmacokinetic and pharmacodynamic modeling, it is predicted at steady-state that the 6 mg/kg/week dose will induce dystrophin expression greater than 30 percent of control. The 3 mg/kg/week dose was chosen as modeling predicts 3 mg/kg/week of GSK2402968 will produce dystrophin expression in the range of 18-22 percent. Potential variability between subjects could theoretically produce higher expression and lead to a dystrophin level correlated with clinical improvement. Weekly injections will be administered for 24 weeks followed by a post-treatment phase. The purpose of the post-treatment phase is to determine the half-life of dystrophin expression due to drug, assess maintenance of functional response due to drug, and provide information about resolution of adverse event and laboratory abnormalities following cessation of treatment. Male participants must be between 5-18 years of age, able to walk, rise from the floor without aids, and have a mutation for which skipping exon 51 would predict restoration of the reading frame (deletion of exons 13-50, 29-50, 43-50, 45-50, 47--50, 48-50, 49-50, 50, or 52). Travel funds are available. View Research Study Flyer.

Related Links:

Magnetic Resonance Imaging and Spectroscopy Biomarkers for Facioscapulohumeral Muscular Dystrophy

Johns Hopkins IRB Protocol Number: NA_00065256
Principal Investigator: Kathryn Wagner, MD, PhD

This study, supported by the FSH Society, will utilize magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to develop non-invasive, quantitative imaging biomarkers for facioscapulohumeral muscular dystrophy (FSHD), a genetic disorder that causes progressive skeletal muscle atrophy. The primary objective of this protocol will be to perform muscle MRI and MRS on groups of subjects with FSHD and control subjects. The imaging protocols employed in this study will be developed in a collaborative effort between resarchers at the Center for Genetic Muscle Disorders at the Kennedy Krieger Institute and Department of Radiology and Radiological Sciences at Johns Hopkins Hospital. Imaging and spectroscopic measurements will be correlated with muscle strength testing measurements to identify biomarkers that accurately reflect disease severity. In order to confirm that these biomarkers are specific for FSHD, both healthy and diseased controls will be enrolled. The successful characterization of imaging and spectroscopy biomarkers in FSHD will provide a powerful, non-invasive tool for future therapeutic trials in FSHD. Travel funds are available. View Research Study Flyer.

For More Information

If you are interested and would like more information about the clinical research studies, contact Genila Bibat, MD, at bibat@kennedykrieger.org or call (443) 923-2778.

Laboratory Research:

Mice in the Lab

 

Dr. Kathryn Wagner and colleagues in the Center's laboratory are focused on skeletal muscle regeneration. Muscle contains resident adult stem cells, which can be stimulated under the appropriate conditions to regrow injured muscle. However, in disease states, muscle frequently takes a non-productive path towards fibrosis or scar tissue instead of regeneration. Several of the factors that determine regeneration versus fibrosis are studied in the laboratory, including myostatin. Myostatin is a negative regulator of muscle growth which, when inhibited, leads to enhanced muscle regeneration and reduced fibrosis. Dr. Wagner and colleagues have shown that myostatin inhibition improves several of the features of the dystrophic mdx mouse model and that loss of myostatin in humans is associated with increased muscle mass. Furthermore, they have demonstrated that inhibition of myostatin stimulates muscle stem cells, dramatically improving muscle regeneration while reducing fibrosis. Their work has led to the development of myostatin inhibitors by several pharmaceutical companies.

Current studies in the laboratory are centered on understanding the potential of myostatin to not only reduce, but reverse pre-existing fibrosis and the potential of myostatin and other factors to act synergistically. Our active collaborations with colleagues in industry facilitate these studies and lead to the direct translation of mouse studies to human trials.