Duchenne Muscular Dystrophy


WHAT'S THE PROBLEM? Cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD) – a fatal X-linked genetic disorder impacting 1:3800 boys. DMD is characterized by progressive muscle weakness and pediatric onset cardiomyopathy. Because symptom recognition is difficult in non-ambulatory patients, clinical evidence of cardiac dysfunction is frequently limited to imaging findings when severe or end-stage cardiomyopathic change has occurred. Conventional late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling (i.e. fibrosis), but it is often a late finding (mean onset observed at 15.2 ± 5.1 years ) in the DMD disease process. Importantly, a biomarker capable of detecting early myocardial remodeling prior to LGE can significantly improve the care of boys with DMD.

WHAT'S OUR SOLUTION? We developed a 3T cardiac MRI exam to identify biomarkers of early cardiac dysfunction to improve patient care and assist in the evaluation of novel therapeutics. Our 3T CMR exam will evaluate functional (i.e. circumferential strain (Ecc) from tagging and DENSE sequences) and microstructural (i.e. pre- and post-contrast T1 mapping) biomarkers. We aim to identify CMR biomarkers that can: 1) identify the specific boy with the early signs of cardiac involvement before LGE; 2) track the progression of DMD within each boy; and 3) show good measurement reliability

FUTURE WORK: The DMD project continues to enroll both healthy controls and boys with DMD to further understand the cardiac MRI signature for myocardial remodeling. Additionally, we aim to determine the biomarkers capable of detecting progressive myocardial changes in the DMD disease progression.

PEER-REVIEWED JOURNAL PAPERS:

1.     Magrath P, Maforo NG, Renella P, Nelson SF, Halnon N, Ennis DB. Cardiac MRI Biomarkers for Duchenne Muscular Dystrophy. Biomarkers in Medicine. 2018 Nov 30. doi: 10.2217/bmm-2018-0125

2.     Maforo NG, Magrath P, Moulin K., Shao J., Kim G., Prosper A., Renella P., Wu H.H., Hanon N., Ennis D.B. T1 mapping and extracellular volume in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T. JCMR 2020 {Submitted}.

3.    Dual SA, Maforo N, McElHinney DB, Prosper A, Wu HH, Maskatia S, Renella P, Halnon N, Ennis DB. Right Ventricular Function and T1-mapping in Boys with Duchenne Muscular Dystrophy. JCMR 2020 {Submitted}.

DMD TEAM:

Nyasha Maforo
Graduate Student - NSF Fellow

Nyasha Maforo

PH.D. STUDENT, UCLA PHYSICS AND BIOLOGY IN MEDICINE, ADMITTED FALL 2016

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Zhan-Qiu Liu, Ph.D.
Postdoc

Zhan-Qiu Liu, Ph.D.

POSTDOCTORAL RESEARCH FELLOW, RADIOLOGICAL SCIENCES LABORATORY

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Seraina Dual, Ph.D.
Postdoc - Swiss NSF Fellow

Seraina Dual, Ph.D.

POSTDOCTORAL RESEARCH FELLOW, CARDIOTHORACIC SURGERY

Stanford Profile