By Laura Hagerty, Ph.D., MDA’s DMD Scientific Program Officer
On September 7, 2015, MDA will rally alongside our Duchenne muscular dystrophy (DMD) community — kids, adults, families, caregivers and others — as we recognize World Duchenne Awareness Day. And as we move toward that day, there’s a palpable feeling of excitement in the air. For the first time ever, we’re awaiting potential approval by the U.S. Food and Drug Administration (FDA) for two drugs to treat not only symptoms but the genetic defect that causes DMD.
But even as we await the FDA’s decision, MDA isn’t slowing down for a second. For the families we serve, treatments and cures can’t come soon enough. That’s why I’m excited to share with you some exciting research news.
MDA has announced the award of 36 new research and development grants, totaling nearly $10 million, to fight muscular dystrophy, ALS (amyotrophic lateral sclerosis) and related diseases that limit muscle strength and mobility. Eight of these new grants, with a combined funding commitment of more than $2 million, are supporting DMD research projects. The new grants bring MDA’s total current funding commitment to DMD research to $16.7 million.
To learn more about the new grants, please read below. In addition, I hope we can count on your continued support for MDA’s efforts to find treatments and cures. It’s only through the generous support of the public and our MDA community that MDA can continue to make critical research like this possible.
All eight of the new research projects supported by the new grants focus on increasing understanding about the processes underlying DMD.
In addition, they aim to:
- identify biomarkers to better track DMD disease progression and improve clinical trial readiness;
- improve DMD standards of care; and
- accelerate development of treatments.
Identifying biomarkers for clinical trials
Four of the new research projects focus on identifying biomarkers — biological indicators that can help track progression of disease and, importantly, signify whether or not an experimental drug is having any effect. Biomarkers are essential for clinical development of drugs, especially since the U.S. Food and Drug Administration (FDA) recently requested that the field identify more biomarkers for DMD trials.
James Ervasti, professor in the department of biochemistry, molecular biology & biophysics at the University of Minnesota in Minneapolis, is developing methods of identifying non-invasive biomarkers that can be measured in all patients across the entire spectrum of DMD disease severity. With colleagues, Ervasti will measure metabolites in a large group of DMD patients and in several different mouse models of DMD to compare the metabolite levels with disease severity. The studies could provide new insight into the skeletal muscle dysfunction in DMD patients and identify new biomarkers that significantly improve clinical trial design and assessment while opening clinical trials to non-ambulatory DMD patients.
Yetrib Hathout, associate professor in the department of integrative systems biology at Children’s National Medical Center in Washington, D.C., is developing a panel of molecular biomarkers, detectable in blood, for DMD. If successful, these biomarkers could help clinicians monitor progression of the disease and determine whether a drug or treatment is working. In addition, they may shed light on the molecular mechanisms of muscle degeneration and point the way toward new therapeutic strategies.
Donghoon Lee, a research associate professor in the department of radiology at the University of Washington in Seattle, is developing imaging biomarkers for DMD. Lee will develop noninvasive magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methodologies that reflect specific underlying tissue and cellular events associated with degeneration and regeneration in muscular dystrophy. Since the equipment used for MRI and MRS is widely available and used in clinical practice, advances in the application of these techniques could quickly lead to improvements in outcome measures for clinical trials in DMD.
Also working to identify biomarkers for DMD is Rebecca Willcocks, an adjunct research assistant scientist in the department of physical therapy at the University of Florida in Gainesville. Willcocks is using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to describe how DMD affects the shoulder, upper arm and forearm muscles of boys, ages 9 to 18 years, with DMD. She also will examine the relationship between MRI and MRS measurements in the arm muscles and arm function (reaching, grasping and moving objects). If the MRI and MRS measures are sensitive to the state of the disease and predictive of functional performance, they may be useful in evaluating the impact and effectiveness of potential therapies in nonambulatory boys and men in clinical trials.
Improving standards of care in DMD
DeWayne Townsend, assistant professor at the University of Minnesota in Minneapolis, is studying the role of oxygen in the DMD-affected heart. With this work, Townsend aims to determine whether decreases in oxygen (called hypoxia) are especially injurious to the heart in DMD, as cells affected by the mutation that causes DMD may use oxygen less efficiently, have difficulty generating energy at low oxygen levels, and be more susceptible to damage following even normally tolerated stresses. The presence of a significant role for hypoxia in the progression of DMD-associated cardiomyopathy (a leading cause of death in DMD) would have a direct impact on decisions about when to initiate ventilator support.
Moving toward treatments
Dada Pisconti, at the University of Liverpool, United Kingdom, is studying how the environment established by fibrosis and inflammation affects the maintenance and regenerative properties of muscle stem cells in DMD. Pisconti will work to determine whether serine protease inhibitor proteins are involved in the DMD disease process. If successful, these studies could lead to a fast development opportunity for therapy, because drugs targeting serine protease activity exist and might be rapidly repurposed.
Thomas Rando, at Palo Alto Veterans Institute for Research and Stanford University in California, is developing a mouse model — a so-called “reporter mouse” — that will reflect and quantify degeneration of skeletal muscles. Importantly, scientists will be able to use the mouse to test the ability of cell and gene therapies to alter the progression of DMD and other muscular dystrophies.
Natassia Vieira, an investigator at Biosciences Institute, University of São Paulo – São Paulo, Brazil, is studying a genetic mechanism that appears to compensate for mutations in the gene that causes DMD. Vieira will study the mechanism by which overexpression of a protein called Jagged1 protects dogs and fish carrying a DMD-causing mutation from exhibiting the typical symptoms and progression of the disease. She aims to validate the mechanism as a new and potentially very exciting drug target for DMD.
At MDA, we’re driving research to its limits every day to get safe and effective treatments and cures on the market and available to our families who so urgently need them. That’s why this round — and every round — of grants is a welcome addition to MDA-supported research currently being conducted in the labs of the best and brightest scientists around the world.
With this new round of grants, we continue to lead the way in advancing frontline discoveries and moving ever closer to cures.
Please visit mda.org to learn more.
Laura Hagerty, Ph.D.
MDA Scientific Program Officer