MDA has awarded a research grant totaling $387,228 over three years to Lisa Baumbach, associate professor in the departments of neurology, pediatrics and biochemistry at the Miller School of Medicine at the University of Miami. The funds will help Baumbach continue to search for disease-causing genes responsible for infantile (either X-linked or type 1) spinal muscular atrophy (SMA).

X-linked SMA is one of a group of disorders with a wide spectrum of overlapping characteristics that involve the muscle-controlling lower motor neurons. As a group, these diseases are known as infantile lower motor neuron diseases (ILMD). They manifest just prior to birth or in the newborn period, and generally are lethal.

The only identified causal gene for X-linked SMA is UBE-1, but it's suspected there may be others that have yet to be identified in the ILMD group.

Baumbach's new research focuses on finding additional disease genes and biological pathways responsible for causing X-linked SMA and the ILMD group of disorders, and on identifying potential genetic modifiers of the causal genes.

Favorable results could have implications for improving early disease detection and paving the way toward potential therapies.

"We are indebted to MDA staff, MDA supporters and the Board of Directors for their ongoing support," Baumbach said.

Funding for this MDA grant began August 1, 2011.

Alan Beggs, a professor of pediatrics at Harvard Medical School and director of the Manton Center for Orphan Disease Research at Children's Hospital Boston, has been awarded an MDA grant totaling $396,990 over three years. The funds will help support Beggs' research on the molecular genetics of congenital myopathies.

These are a diverse group of inherited neuromuscular conditions that include myotonia congenita, paramyotonia congenita, central core disease (CCD), nemaline myopathy, myotubular myopathy (MTM) and other centronuclear myopathies (CNM), periodic paralysis (PP), and others, including some that have not yet been identified.

They all result from defects in skeletal muscle that lead to weakness or abnormalities of muscle contraction of variable onset and severity.

Beggs and his colleagues have built an extensive data registry and repository of samples from patients and their families, supported in part by MDA.

"This repository has led to the identification of the underlying gene defect for many individuals," Beggs said. "However, the responsible genes for up to half the cases remain unknown."

Beggs has now started screening for congenital myopathy-causing mutations in zebrafish and has discovered mutations in several genes that may be related to human neuromuscular diseases.

In this new project, Beggs and colleagues will determine the nature of these new gene mutations and their relationships to the muscle defects seen in the fish. They'll then use this information to identify people with analogous muscle findings, in whom they will analyze the genes identified in the zebrafish.

The affected fish also will allow the investigators to test drugs and other interventions to treat congenital myopathies.

"In 1996, MDA provided my very first grant to study muscle development and function," Beggs said, "and ever since then, it has been a constant source of support and encouragement for my efforts to understand and treat congenital myopathies."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $404,274 over three years to Stephen Cannon, professor of neurology and associate dean for undergraduate medical education at the University of Texas Southwestern Medical Center in Dallas. The funds will help support Cannon’s research into attacks of paralysis in people with periodic paralysis (PP).

Periodic paralysis is a muscle disorder in which affected individuals have transient attacks of muscle weakness lasting hours to days.

With prior support from MDA, Cannon and colleagues generated a mouse model for hypokalemic periodic paralysis, in which attacks are triggered by low blood potassium levels. Using the new mouse model, the team intends to establish how shifts in potassium level, exercise and stress trigger attacks of weakness.

Preliminary work already has identified several strategies to reduce the risk of an attack or to reduce the severity of weakness, through the use of available drugs or by modifying the level of muscular activity.

“Support from the MDA has been a vital component of our research program on myotonia and periodic paralysis for two decades,” Cannon said. “MDA’s commitment to funding investigation into the fundamental biology of these diseases has yielded many important advances.

“Through the generosity of donors and the wisdom of the MDA Board of Directors, important work on muscle disease has been able to not only continue, but also to flourish.”

Funding for this MDA grant began August 1, 2011.

Martin Childers, a professor at the Institute for Regenerative Medicine in Winston-Salem, N.C., has been awarded an MDA grant totaling $480,000 over three years. The Institute is part of Wake Forest University Baptist Medical Center.

The new funds will help support Childers' research on heart disease associated with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD results from a complete lack of dystrophin protein in skeletal and cardiac muscles, and BMD results from the presence of partially functional dystrophin protein. Both diseases are caused by mutations in the dystrophin gene.

"Many patients with DMD die as young adults from heart failure," Childers said. "The reason for this is that the heart muscle carries a genetic mutation that damages the normal operation of this all-important muscle. Our project will allow for the discovery of new drugs that might reverse or prevent the effects of the disease on the heart muscle."

Childers and colleagues will use two types of new technology to find potential new drugs for heart disease related to dystrophin deficiency. First, they'll use a method called cellular "reprogramming" to create heart cells from the skin cells of DMD patients. "This remarkable new technology will allow us to study how a genetic mutation affects the heart cells of a specific patient," Childers said.

The second method the investigators will employ is a drug-discovery "platform" that can screen thousands of compounds in individual cells.

"By marrying these two incredible technologies, this project will allow, for the first time, the testing of new drugs directly on the heart cells of an individual patient without any risk to the patient," Childers noted.

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $429,983 over three years to Don Cleveland, departmental chair of cellular and molecular medicine; professor of medicine, neurosciences, and cellular and molecular medicine; and member of the Ludwig Institute for Cancer Research in La Jolla, Calif. The funds will help support Cleveland’s research into the connection between mitochondria and ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

Mitochondria, the intracellular compartments that consume oxygen to produce chemical fuel that supports the cell, have been implicated as targets for toxicity in the inherited, SOD1-associated forms of ALS.

It is not known, however, in which cell types of the nervous system mitochondrial damage occurs, whether the ensuing mitochondrial dysfunctions are a cause or a consequence of neuronal degeneration during the disease and if the effects are the same in SOD1-associated ALS caused by different SOD1 mutations.

Using mice that are genetic mimics of inherited, SOD1-related ALS, Cleveland intends to determine at what disease stage and in which cell types of the central nervous system mitochondrial dysfunction occurs, and whether rescue of individual mitochondrial functions or an increase in mitochondrial activity may alter the ALS disease course.

“This comparative analysis will, in principle, provide a test for whether mitochondria are a common target of toxicity,” Cleveland said.

Funding for this MDA grant began August 1, 2011.

Peter Currie, a professor of medicine at Monash University in Clayton, Victoria, Australia, was awarded an MDA research grant totaling $375,000 over three years. The funds will help support Currie's research, which involves screening for possible therapeutic molecules using the zebrafish model of Duchenne muscular dystrophy (DMD).

The underlying cause of DMD is an absence of the muscle protein dystrophin due to any of a large number of mutations in the dystrophin gene. Becker muscular dystrophy (BMD), a less severe form of MD, is caused by dystrophin gene mutations that result in production of a partially functional dystrophin protein.

"While the current animal models of DMD have generated valuable insights into the pathological basis of the disease, each has their limitations," Currie notes. "We have isolated mutations in the zebrafish dystrophin gene and have determined that dystrophin-deficient zebrafish accurately model the human condition."

In this new project, Currie and his colleagues will undertake a drug screen for small molecules that can inhibit the onset of signs of muscular dystrophy in the dystrophin-deficient zebrafish.

"MDA funding has been critical in allowing me to pursue modeling muscular dystrophy in zebrafish," Currie said. "There is simply no way that the research that has happened around muscle disease modeling in my laboratory would have occurred at the pace that it has without the generous support of MDA."

Funding for this MDA grant began August 1, 2011.

Diego Fraidenraich, an assistant professor in the department of cell biology & molecular medicine at the University of Medicine and Dentistry of New Jersey, was awarded an MDA grant totaling $375,000 over three years. The funds will support his study of the relationship between muscle and fat formation in a mouse model of Duchenne muscular dystrophy (DMD).

These mice, like humans with DMD, lack the dystrophin protein in their skeletal muscles and heart because of a mutation in the dystrophin gene. They develop a muscle disease resembling human DMD.

Recently published reports have shown that skeletal muscle and fat have a common cellular ancestor, and Fraidenraich's team intends to understand the similarities and differences in the development of these two tissues.

In previous experiments, Fraidenraich and colleagues treated DMD mice with stem cells from healthy mice, so that the dystrophin protein was present in some, but not all, of their cells.

These so-called "mosaic" mice developed some normal muscle tissue from the stem cells, as well as some fat tissue that had muscle-like characteristics. The researchers termed this unusual, stem-cell-derived tissue "muscularized fat."

In his new work, Fraidenraich will seek to understand more about this muscle-like fat derived from the transplanted stem cells and define its possible role in the development of muscle. He'll also try to increase the ratio of muscle to fat in the DMD mice.

Fraidenraich hopes to provide new understanding of muscle formation that will supply leads for future therapies for DMD and perhaps other forms of muscular dystrophy.

He has received MDA funding since 2007, and says, "Continuous funding from MDA has allowed me to develop and expand my research program. The support has been instrumental to my research and my lab."

Funding for this MDA grant began August 1, 2011.

Alfred Goldberg, professor or cell biology at Harvard Medical School in Boston, has received an MDA research grant totaling $410,777 over three years to continue research into the mechanisms underlying muscle atrophy, with particular relevance for limb-girdle muscular dystrophy (LGMD) and possibly inclusion-body myositis (IBM).

In his previous work, Goldberg has helped clarify the general mechanisms of muscle atrophy resulting from motor neuron disease, inactivity, various systemic diseases and myopathies.

Goldberg and his research team will focus now on mechanisms that normally inhibit a protein called FoxO, which has been implicated in stimulating muscle protein breakdown.

Of particular interest to the team are two proteins, PGC1-alpha and SIRT1, both of which previously have been shown to inhibit FoxO function.

Further studies of these and other proteins' protective mechanisms could suggest new ways of combating muscle degeneration and atrophy.

"Over the years, my laboratory has received generous support from the Muscular Dystrophy Association, which has made possible a number of important findings about protein metabolism in muscle, and specifically about the mechanisms of muscle atrophy," Goldberg said. "My colleagues and I are very grateful for the support."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $202,508 over a period of three years to Raymond Grill, assistant professor in the department of integrative biology and pharmacology at the University of Texas Health Science Center, Houston. The funds will support testing in the SOD1 mouse model of an experimental combination drug treatment in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

One process suspected to be heavily involved in ALS disease progression is inflammation, which can create a toxic environment and kill motor neurons.

Using the SOD1 ALS research mouse model, Grill's research team will test the hypothesis that a drug called Licofelone, which has completed phase 3 testing in humans, will enhance the ability of riluzole (Rilutek) to better penetrate the nervous system. (Rilutek is the only drug approved by the U.S. Food and Drug Administration for treatment of ALS.)

The researchers expect the combination treatment will reduce inflammation, protect motor function, rescue motor neurons and prolong survival in the SOD1 mice, and if favorable results are obtained, the group will attempt to "fast-track" the "two-part" treatment into clinical development.

"The support provided by the Muscular Dystrophy Association provides an invaluable opportunity for laboratories such as ours to enter this important field and both test and translate new ideas."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a grant totaling $384,066 over three years to Emanuela Gussoni, an assistant professor in the division of genetics and program in genomics at Children's Hospital Boston and Harvard University. The grant will support Gussoni's studies to improve the efficacy of stem cell transplantation as a strategy to treat Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and possibly other forms of muscular dystrophy.

The direct injection of normal muscle stem cells into mice and people with muscular dystrophy has been attempted as a way to provide missing proteins to muscle tissue. (In DMD, the dystrophin protein is missing; in BMD, it's present but only partially functional.)

However, Gussoni said, studies have shown that, while the technique is safe in patients, their muscles have not shown significant improvement. One of the causes for the lack of improvement is the rapid death of the normal cells following transplantation.

To overcome this problem, different cell types more capable of surviving the transplant and producing the desired proteins must be identified. Gussoni's research team has found that human cells that produce a surface protein called MCAM can form muscle in tissue culture and following injection into animals.

If they live up to the preliminary expectations of Gussoni and her colleagues, MCAM-expressing cells could become candidates for cell transplantation to treat MD.

"MDA funding has been instrumental throughout my career," said Gussoni, who has received several MDA grants. "MDA develops and fosters both new and established investigators who are highly committed to improving the lives of people with muscle disorders."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $375,000 over a period of three years to Susan Hamilton, L.F. McCollum Chair in Molecular Physiology, department of molecular physiology and biophysics at Baylor College of Medicine in Houston. The funds will help support Hamilton’s study of the molecular mechanisms underlying a wide spectrum of muscle disorders including central core disease (CCD) and malignant hyperthermia (MH).

CCD is caused by mutations in the cellular internal calcium release channel (the ryanodine receptor, or RYR1), which lead to an abnormality of calcium release from deep inside muscle fibers, and selective destruction of the cellular energy factories called mitochondria.

Malignant hyperthermia, closely associated with CCD, manifests as a sustained, life-threatening muscle contraction event triggered by certain types of anesthetics, some muscle relaxants or sometimes elevated temperatures.

Using a research mouse model that carries a mutation in the RYR1 gene, Hamilton’s research team will work to identify the processes that lead to mitochondrial destruction in CCD and environmental temperature sensitivity in malignant hyperthermia, with a special focus on the links between mitochondria and the intracellular calcium stores controlled by RYR1.

“MDA has played a major role in my career, beginning with a postdoctoral fellowship many years ago,” Hamilton said. “This fellowship supported my first foray into muscle research and led to my career-long commitment to studying skeletal muscle and skeletal muscle diseases.”

Funding for this MDA grant began August 1, 2011.

Samantha Harris, an associate professor in the department of neurobiology, physiology and behavior at the University of California, Davis, has been awarded an MDA grant totaling $244,024 over two years. The funding will help Harris in her quest to determine the properties of a skeletal-muscle protein called myosin binding protein C.

Mutations in the gene for myosin binding protein C affect muscle contraction and could play a role in a number of muscle diseases.

"MDA support of this work comes at a pivotal time," Harris said, "not only for the opportunity it provides for making rapid inroads into our understanding of [muscle contraction abnormalities], but also for the opportunity it provides in opening up new research directions for my lab by fostering new collaborations. I am eager to get started!"

Funding for this MDA grant began August 1, 2011.

MDA awarded $294,183 over three years to Vasanthi Jayaraman, an associate professor in the department of biochemistry and molecular biology at the University of Texas Health Science Center in Houston. The funds will help support Jayaraman’s study of the molecular mechanisms underlying motor neuron death in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

Jayaraman is particularly interested in a type of glutamate receptor known as calcium-permeable AMPA receptors. These cause toxicity and are thought to be a major trigger for selective motor neuron death and the resulting loss of muscle control in ALS.

Although AMPA receptor inhibitors have been shown to consistently decrease neuronal death in experimental models and increase survival time in a mouse model of ALS, they’ve not been tried in the clinic.

The challenge her research team has taken on, Jayaraman said, is to develop AMPA receptor antagonists that prevent activation of the calcium-permeable AMPA receptors without causing harmful side effects or affecting the function of other subtypes of glutamate receptors.

“With the funds provided by the Muscular Dystrophy Association,” Jayaraman said, “we are in a position to show the feasibility of these projects, which we believe will have high rewards in terms of being able to develop therapeutic agents toward ALS.”

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $379,500 over three years to Tejvir Khurana, a professor of physiology at the University of Pennsylvania. The grant will support Khurana's research to increase the production of utrophin, a protein that may improve muscle strength and function in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

Studies suggest that utrophin can, at least in part, substitute for the dystrophin protein missing in DMD and only partially functional in BMD. A mutation in the dystrophin gene is the root cause of both diseases.

Since functional utrophin is produced in the muscles of people with DMD and BMD, therapies based on supplying more of it are unlikely to cause an unwanted immune response. In contrast, therapies based on supplying functional dystrophin, which many people with DMD/BMD do not produce, may cause an unwanted immune response to this protein.

Khurana's strategy for increasing utrophin production is based on removing a biological "brake" that represses it.

"We have found that utrophin is in a state of repression," Khurana said, "and that a class of molecules called microRNAs cause this repression. We will develop methods to 'repress the repressors' and hence achieve utrophin upregulation."

Khurana and colleagues will test their strategy in dystrophin-deficient mice that develop a DMD-like disease.

Funding for this MDA grant began August 1, 2011.

Jasna Kriz, associate professor in the department of psychiatry and neuroscience at Laval University, Quebec City, Canada, was awarded an MDA research grant totaling $445,086 over a period of three years to help refine and describe a new mouse model that will enable scientists to visualize different aspects of the disease process in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

Previously, Kriz and colleagues developed mouse models with bioluminescent and fluorescent genes (from fireflies) that allow researchers to visualize ALS-related events such as neuroinflammation and neuronal damage in the brains and spinal cords of living mice. They even were able to detect distinct and disease-specific signals linked to presymptomatic stages of the disease.

Now, Kriz plans to use the previously generated models to generate ALS imaging reporter mice, which will enable scientists to visualize, in live mice, different elements of the ALS disease process.

Once their characteristics are fully understood, the ALS reporter mice will represent a unique tool that will allow scientists to study the ALS disease process and real-time response to experimental therapies.

Favorable results are expected to lead to more efficient translation of experimental therapies to the clinic and new therapeutic strategies for ALS.

Funding for this MDA grant began August 1, 2011.

MDA awarded a research grant totaling $375,000 over three years to Michael Kyba, assistant professor in the Lillehei Heart Institute and department of pediatrics at the University of Minnesota in Minneapolis. The funds will help support Kyba's efforts to identify and test experimental therapies in facioscapulohumeral muscular dystrophy (FSH, or FSHD).

The mutation associated with FSHD is a contracted (deleted) segment of DNA in a region of chromosome 4 called D4Z4. The D4Z4 region consists of a series of repeated DNA sequences. It is not yet fully understood how the contraction causes the disease, but scientists have found that it appears to modify the packaging of this part of chromosome 4 so that a gene named DUX4, which is encoded within each D4Z4 repeat, becomes active.

Kyba and colleagues are developing mice that carry the DUX4 gene. The team aims to identify and test drug- and genetic-based inhibitors of DUX4 in the mice, the most promising of which potentially may lead to experimental therapies for FSHD.

"This research project is directed at developing a treatment for FSHD," Kyba said. "As MDA is dedicated to curing muscular dystrophy, this is a natural partnership. Support from MDA is critical to our success."

Funding for this MDA grant began August 1, 2011.

Clotilde Lagier-Tourenne, a postdoctoral fellow at the University of California, San Diego, in La Jolla, was awarded an MDA development grant totaling $180,000 over a period of three years to study the roles of two proteins, TDP43 and FUS, in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

ALS-causing mutations in the genes for two RNA binding proteins, TDP43 and FUS, appear to cause disruption in the processing of RNA (the chemical step that directs protein synthesis).

In a research mouse model, Lagier-Tourenne and colleagues have identified RNAs that TDP43 normally binds to, as well as abnormalities in the processing of RNA that occur when TDP43 is depleted.

Similarly, in their new work, the researchers plan to determine the role of FUS in the regulation of RNA in the mouse central nervous system.

The team's proposed set of studies is expected to identify a set of alterations to normal RNA processing that will define a TDP43- and FUS-dependent ALS disease signature.

"I am really grateful for the support from MDA," Lagier-Tourenne said. "It represents strong encouragement at this stage of my career and will allow me to extend my research on the role of RNA processing in neurodegeneration."

Funding for this MDA grant began August 1, 2011.

Clotilde Lagier-Tourenne, a postdoctoral fellow at the University of California, San Diego, in La Jolla, was awarded an MDA development grant totaling $180,000 over a period of three years to study the roles of two proteins, TDP43 and FUS, in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

ALS-causing mutations in the genes for two RNA binding proteins, TDP43 and FUS, appear to cause disruption in the processing of RNA (the chemical step that directs protein synthesis).

In a research mouse model, Lagier-Tourenne and colleagues have identified RNAs that TDP43 normally binds to, as well as abnormalities in the processing of RNA that occur when TDP43 is depleted.

Similarly, in their new work, the researchers plan to determine the role of FUS in the regulation of RNA in the mouse central nervous system.

The team's proposed set of studies is expected to identify a set of alterations to normal RNA processing that will define a TDP43- and FUS-dependent ALS disease signature.

"I am really grateful for the support from MDA," Lagier-Tourenne said. "It represents strong encouragement at this stage of my career and will allow me to extend my research on the role of RNA processing in neurodegeneration."

Funding for this MDA grant began August 1, 2011.

Youngjin Lee, postdoctoral associate in the department of neurology at Johns Hopkins University School of Medicine in Baltimore was awarded an MDA development grant totaling $179,997 over three years. The funds will support Lee's study of the role of a protein called MCT-1 in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

One hypothesis to explain the death of motor neurons in ALS suggests that glial cells, whose job it is to provide nerve cells with nourishment and support, do not provide enough necessary energy components called substrates.

One of these substrates, lactate, is delivered to neurons by a type of transporter protein known as MCT-1. Lee’s research team has generated mice specifically designed to help elucidate the activity, regulation and function of MCTs and the protein’s role in neurodegeneration in ALS.

Favorable results could lead to new targets at which to aim therapeutic agents capable of preventing or slowing disease progression.

"Funding by MDA is 'absolutely crucial' for us to understand the balance of energy between motor neurons and their protective glial cells," Lee said, "and to find further therapeutic targets for preventing disease progression in ALS."

Funding for this MDA grant began August 1, 2011.

Jennifer Levy, a postdoctoral research fellow in the department of molecular physiology & biophysics at the University of Iowa Carver College of Medicine, has been awarded an MDA development grant totaling $180,000 over three years. (This type of grant reflects MDA's commitment to the career development of promising young researchers.) The funds will support Levy's research on repair of the muscle-fiber membrane.

Each muscle fiber is surrounded by a membrane that undergoes frequent rounds of damage and repair, assisted by a protein called dysferlin.

Dysferlin is deficient in the type 2B form of limb-girdle muscular dystrophy (LGMD) and the Miyoshi form of distal muscular dystrophy (DD). In these forms of MD, muscle-fiber membrane repair is ineffective and is accompanied by inflammation. However, the relationship between dysferlin deficiency and inflammation is not fully understood.

"I aim to identify the aberrant membrane repair mechanisms that compensate for the loss of dysferlin," Levy said, "and to determine if dysferlin-independent membrane repair signals immune cells to augment inflammation at sites of muscle injury."

She said identifying new factors that contribute to muscle inflammation in dysferlin-deficient patients may also lead to the discovery of new therapeutic strategies for other muscular dystrophies also associated with inflammation.

"MDA is critical to the funding of my research," Levy said. "As I am currently a postdoctoral research fellow, this funding will be beneficial in my development into an independent investigator."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $202,222 over two years to David Lynch, professor of neurology at Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine. The funds will help support Lynch's study of the relationship between diabetes and Friedreich's ataxia (FA).

Some individuals with FA develop severe cardiomyopathy (heart disease), while others also may develop diabetes and a resistance to the effects of the hormone insulin, Lynch said, noting "This phenomenon may have implications for the overall progression of FA and the mechanisms involved in causing the disease."

Lynch and colleagues plan to examine the relative likelihood of people with FA to develop diabetes. The team will use measurements of blood sugar and blood insulin levels to assess which features of FA make a particular individual more likely to have abnormal insulin resistance.

The team will work to identify specific genes that contribute to abnormal insulin resistance in FA and also determine whether frataxin, the protein that is deficient in FA, contributes to the development of insulin resistance and diabetes.

The MDA grant will “support development of the collaborative group of individuals who will contribute to this project, which leverages previous data also developed with MDA support," Lynch said.

Funding for this MDA grant began August 1, 2011.

Paul Martin, a professor of pediatrics and of physiology and cell biology at Ohio State University College of Medicine, has been awarded an MDA grant totaling $396,000 over three years. The award will help support Martin's study of the possible therapeutic effects of an enzyme called GALGT2 in Duchenne muscular dystrophy (DMD).

GALGT2 is involved in adding sugar molecules to a protein called alpha-dystroglycan, part of a cluster of proteins located at the muscle-fiber membrane. This cluster is abnormal in a number of forms of muscular dystrophy.

Among the other proteins normally located in this cluster are dystrophin, which is deficient in DMD and abnormal in the related Becker muscular dystrophy (BMD); alpha-sarcoglycan, which is deficient in the type 2D form of limb-girdle muscular dystrophy (LGMD); and merosin, which is deficient in the type 1A form of congenital muscular dystrophy (CMD).

Previous work in Martin's lab has shown that raising GALGT2 levels can help compensate for the loss of dystrophin in a mouse model of DMD, inhibiting the development of muscle abnormalities in DMD model mice.

The Martin lab also has shown that increasing GALGT2 levels can have therapeutic effects on skeletal muscles in animal models of LGMD2D and CMD1A.

"Because GALGT2 is normally expressed in skeletal muscles," Martin said, "its overexpression may have fewer immunologic issues than gene replacement or exon skipping approaches." (The latter approaches increase levels of proteins that are abnormal or deficient in patients, potentially triggering an unwanted immune response.)

"MDA has played a seminal role in the development of my work," Martin said. "MDA funded two years of my postdoctoral training, provided me with my first research grant as an independent faculty member, and now will provide research funding to translate proof-of-concept studies into potential therapies."

Funding for this MDA grant began August 1, 2011.

MDA awarded a grant totaling $363,672 to Carlos Moraes, professor of neurology at the University of Miami School of Medicine, to study the effects generated by an increase in functional mitochondria (the "energy factories" in cells) in mitochondrial myopathy.

In previous studies, Moraes and colleagues increased the production of new mitochondria (a process called "mitochondrial biogenesis") in the cells of mice with a disease resembling mitochondrial myopathy. The mice, which began receiving treatment during the embryonic stage of development, exhibited improved symptoms and prolonged life.

As part of their new work, Moraes and his team will test various methods, alone and in combination, of increasing production of mitochondria in adult mice with a disease similar to human mitochondrial myopathy. The investigators also will study whether endurance-based exercise increases production of mitochondria.

"This project may lead to improved treatment for mitochondrial myopathies," Moraes said.

Funding for this MDA grant began August 1, 2010.

MDA has awarded a research grant totaling $278,570 over three years to Jasprina Noordermeer, a professor in the department of molecular cell biology at Leiden University Medical Center in the Netherlands. The grant will support Noordermeer's studies of the role of dystrophin in the brain. The dystrophin protein is absent or deficient in boys with Duchenne muscular dystrophy (DMD).

The role of dystrophin in skeletal muscles is fairly well-understood, and its absence in DMD leads to the progressive weakness seen in this disease. A great deal is also known about the role of this protein in cardiac muscle, where its absence leads to cardiac muscle abnormalities (cardiomyopathy) in DMD.

It's also known that dystrophin is normally present in the brain, and that at least some DMD patients have cognitive disabilities. However, little is known about the role of dystrophin or the effects of dystrophin deficiency in the brain.

Ultimately, Noordermeer says, treatments for DMD should reverse both muscle loss and the cognitive deficits associated with this disease, but how the lack of dystrophin results in defects at the connections ("synapses") where nerve cells interact with each other is unclear.

She and her colleagues will study the role of dystrophin and dystrophin deficiency in the brain in dystrophin-deficient flies and mice.

"MDA funding is critical to allow us to further our understanding of the functions of dystrophin and its [molecular] partners at the synapse," Noordermeer said. "We particularly appreciate MDA's commitment to funding research in model organisms directed toward unraveling DMD-associated dysfunctions."

Funding for this MDA grant began August 1, 2011.

MDA awarded a research grant totaling $329,091 over two years to Kristen Nowak, an associate professor at the University of Western Australia in Perth, and the Western Australian Institute for Medical Research. The funds will support Nowak's study of diseases caused by defects in the skeletal muscle actin gene, which include "essentially any genetic neuromuscular disease that tends to be severe in some patients and mild in others." 

Nowak's team will concentrate on development of a therapy for people with skeletal muscle actin diseases, while also looking for genetic modifiers of disease severity.

Using a research mouse model with severely affected skeletal muscle, the researchers will search for modifying genes that activate cardiac (heart) actin, or any other gene able to rescue the mice through another mechanism.

"Identified genes will become the focus of future studies determining how to utilize them to formulate treatments," Nowak said.

Nowak acknowledged the importance of MDA funding in both previous and current work.

"Being able to continue this work with the current project is of utmost importance, not only for patients with skeletal muscle actin disease and their families, but hopefully for people with other neuromuscular diseases as well."

Funding for this MDA grant began August 1, 2011.

Sonja Nowotschin, a postdoctoral research fellow in the developmental biology department at the Sloan-Kettering Institute in New York, has been awarded an MDA development grant totaling $163,638 over three years. (Development grants are MDA's mechanism for furthering the career development of promising young researchers.)

The funding will help support Nowotschin's research on how muscles are formed at the embryo stage, with the goal of understanding and ultimately treating congenital muscular dystrophies (CMDs) and congenital myopathies, such as myotonia congenita, paramyotonia congenita,central core disease (CCD), nemaline myopathy,myotubular/centronuclear myopathies (MTM/CNMs) and periodic paralysis.

Nowotschin and her colleagues will study embryonic mice to investigate the origin and development of the skeletal muscles. They'll identify and study the stem cells that form muscles in mice with and without genetic mutations.

"Knowledge gained from these studies will assist logical efforts to design new therapeutic strategies," Nowotschin said.

"Importantly," she added, "by investigating the molecular mechanisms operating in the embryo, we will be able to formulate the molecular principles that should assist in developing methods to reprogram adult, or 'differentiated,' cells." Cells that have matured (differentiated) into muscle tissue and have then been reprogrammed back into stem cells are being considered as possible therapies to treat muscle disease.

MDA funding, Nowotschin said, "is essential to move this project forward."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a development grant totaling $180,000 over three years to Edward Owusu-Ansah, a postdoctoral fellow in the department of genetics at Harvard Medical School in Boston. The funds will help support Owusu-Ansah's research into the molecular mechanisms underlying mitochondrial myopathies.

A system consisting of five large protein complexes, known as the functional oxidative phosphorylation system, or OXPHOS, plays a crucial role in the generation of energy (ATP) in the cellular power factories known as mitochondria. Disruption of this system results in the compromise of a range of biochemical and metabolic activities in cells, resulting in mitochondrial myopathy.

In a fruit fly research model Owusu-Ansah plans to examine the intracellular signaling that contributes to mitochondrial myopathy, particularly with regard to one of the five larger protein complexes that is part of the OXPHOS system.

"Due to the extensive similarity between fruit fly and human genomes," Owusu-Ansah said, "I anticipate that information obtained from this study should uncover novel therapeutic strategies for alleviating mitochondrial myopathy in humans."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $474,278 over three years to Terence Partridge, a professor of pediatrics at George Washington University Medical School and Children's National Medical Center in Washington, D.C. The award will help support Partridge's work to improve the usefulness of the standard mouse model of Duchenne muscular dystrophy (DMD), the so-called "mdx" mouse.

The mdx mouse lacks dystrophin, the protein that's missing in people with DMD and only partially functional in people with the related disease Becker muscular dystrophy (BMD).

The muscular dystrophy developed by the mdx mouse "closely resembles DMD in some respects," Partridge said, "but differs in others. In order to make the best use of this valuable animal model, we need to fully understand the extent of the similarities and differences, so that we can take them into account when applying information gathered from the mouse to the situation in man."

Partridge and colleagues will develop reliable methods for making accurate and reproducible measurements of the rates of growth, death and regeneration of muscle taking place at different times in the mdx mouse.

"Nowadays, funding from MDA is especially important to those of us working on the interface between science and translational research," Partridge said. "MDA provides for the conduct of research that is fundamental in nature but is aimed at providing information that is directly relevant to the understanding of the disease processes or to the development of therapeutic agents to moderate those disease processes."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $295,269 over three years to Grace Pavlath, professor in the department of pharmacology at Emory University in Atlanta. The new funds will help support Pavlath’s study of abnormal muscle regeneration in the muscular dystrophies, particularly Duchenne muscular dystrophy (DMD).

Pavlath intends to study the abnormal "branched" muscle fibers that sometimes appear as part of the muscle regeneration process after illness or injury. Such fibers have shown characteristic functional abnormalities; they also are weaker and more prone to injury than normal, long cylindrical cells.

Although the exact contribution of branched myofibers to DMD muscle is unclear, muscles containing high levels of branched myofibers are unlikely to function normally. Thus, decreasing the number of branched myofibers likely will be beneficial for improving both muscle physiology, and the efficiency of cell and gene therapy approaches for muscular dystrophy.

Recent work out of Pavlath's lab analyzing the role of MOR23 in muscle regeneration revealed that it's a necessary factor in the proper skeletal muscle regeneration in mice; loss of MOR23 leads to increased myofiber branching.

Using both a healthy mouse and a research mouse model with a DMD-like disease, Pavlath’s team will manipulate two molecules, MOR23 and kirrel12, and examine their roles in regulating myofiber branching in muscle regeneration.

Findings from Pavlath’s work could lead to a clearer understanding of the underlying mechanisms that cause abnormal muscle-fiber branching in regeneration and, in addition, provide biological targets at which to aim future therapies.

"MDA funding has been extremely critical for this and past projects," Pavlath said. "We would not be able to study the mechanisms of myofiber branching without it."

Funding for this MDA grant began February 1, 2011.

MDA has awarded a research grant totaling $330,000 over three years to Maria Pennuto at the Italian Institute of Technology in Genova, Italy. The funds will help support Pennuto's continued studies of the molecular mechanisms underlying spinal-bulbar muscular atrophy (SBMA).

The mutation responsible for SBMA is in the gene for the androgen receptor protein.

Pennuto plans to test the hypothesis that activation of a particular molecule called protein kinase A will reduce accumulation and toxicity of the mutant androgen receptor and help protect the spinal cord in SBMA.

The project capitalizes on results obtained in the last three years from another project supported by MDA.

In that work, Pennuto and colleagues identified another protein kinase that confers protective effects on SBMA-affected skeletal muscle.

The team will use cellular models as well as mouse motor neuron cells and mouse models that express the mutant protein and mimic crucial features of the disease.

"The unique support of MDA has allowed us to pursue the investigation of the molecular mechanisms of SBMA," Pennuto said, noting that she and her research team can use what they've learned to help develop therapeutic approaches for SBMA and other motor neuron diseases.

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $313,551 over three years to Pere Puigserver, associate professor in the department of cancer biology at the Dana-Farber Cancer Institute, and department of cell biology at Harvard Medical School in Boston. The funds will help support Puigserver’s research into the study of two newly identified genes that may increase muscle performance in mitochondrial myopathies.

It’s known that activation of a gene called PGC1-alpha has the potential to be an effective treatment for mitochondrial myopathy in people with neuromuscular disorders, Puigserver explained. But it makes for a difficult “druggable” target.

Puigserver’s research team has identified two new genes, mTORC1 and YY1, that form new “teammates” that stimulate PGC1-alpha and increase healthy skeletal muscle performance. The two genes appear to be easily targeted by small molecules and other drugs.

The team will assess how the mTOR/YY1 complex activates PGC1-alpha, and then will perform a small-molecule chemical screen to identify compounds that activate PGC1-alpha in skeletal muscle cells modified with genetic mutations from people with myopathies.

“The importance of MDA funding for our project is crucial,” Puigserver said, providing “a unique avenue to accelerate research that can impact people with muscle diseases.”

Funding for this MDA grant began August 1, 2011.

MDA has awarded a development grant totaling $180,000 over a period of three years to Fedik Rahimov, a postdoctoral research fellow at the program in genomics at Harvard Medical School and Children's Hospital Boston. The funds will help further elucidate the molecular mechanisms underlyingfacioscapulohumeral muscular dystrophy (FSH, or FSHD).

The mutation associated with FSHD is a contracted (deleted) segment of DNA in a region of chromosome 4 called D4Z4. Although it's not yet fully understood how the contraction causes the disease, it appears to be one of two factors necessary to cause abnormal activation of a gene called DUX4.

The protein produced from the DUX4 gene instructions is toxic to muscle cells, and causes muscle degeneration and weakness.

Fedik and colleagues plan to assess DUX4 activity in FSHD-affected muscles in an attempt to uncover the mechanisms underlying FSHD. It's hoped that understanding and defining these mechanisms may lead to the discovery of disease biomarkers.

"Funding from MDA will help us enormously as we continue our work on biomarker discovery using advanced technologies," Rahimov said. "Data generated from this study will be deposited into public repositories, and the discovery nature of our study will allow the generation of new hypotheses to test for new therapeutic targets."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $602,087 over three years to Thomas Rando, a professor in the department of neurology and neurological sciences at Stanford (Calif.) University School of Medicine. The grant will help support Rando's studies to understand how scar-tissue formation (fibrosis) occurs in muscular dystrophies, especially Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is caused by an absence of the dystrophin protein, and BMD is caused by dystrophin protein that's only partially functional.

In skeletal muscles affected by muscular dystrophy, fibrosis develops as muscle fibers degenerate and are replaced by connective tissue.

"The goals of my experiments are to understand why fibrosis occurs in the muscular dystrophies and to determine the biochemical mechanisms that lead to it," Rando said.

"We have preliminary data that suggest that a specific biochemical pathway known as the TGF-beta signaling pathway is activated in dystrophic muscle and affects muscle stem cells in a way that leads to the development of fibrosis."

Rando and colleagues will directly test whether blocking this pathway leads to a reduction of fibrosis in the muscles of dystrophin-deficient mice that develop a DMD-like disease.

"These studies have the potential to lead directly to new therapies that will reduce the amount of fibrosis in the muscles of boys with Duchenne muscular dystrophy," Rando said.

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $625,959 over a period of three years to Des Richardson, professor and senior principal research fellow at the University of Sydney (Australia) School of Medical Sciences. The funds will help support Richardson's continued research into iron metabolism in Friedreich's ataxia (FA).

The aim of Richardson's studies is to examine the role of altered iron metabolism in the cellular energy factories called mitochondria.

Using molecular and cellular models, as well as a research mouse model that closely mimics the neurodegeneration and heart problems observed in people with FA, Richardson and colleagues will test a variety of strategies designed to help elucidate the function of frataxin, the protein that’s deficient in this disease.

The team also will test a new experimental therapy designed to replace or bypass the function of frataxin by getting iron to the mitochondria in a form that can be easily utilized for the processes that are lacking when frataxin levels are inadequate.

"We gratefully acknowledge MDA funding," Richardson said. "The knowledge of these alterations is critical for developing new therapeutics that could replace the function of this molecule in patients."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a grant totaling $375,000 over three years to Michael Rudnicki, director of the Regenerative Medicine Program at Ottawa Hospital Research Institute and a professor in the department of medicine at the University of Ottawa, Canada. This funding will support Rudnicki's continuing studies on the function of muscle satellite cells in mice with a disease resembling human Duchenne muscular dystrophy (DMD).

DMD is caused by any of a number of mutations in the gene for the muscle protein dystrophin that result in a complete absence of the dystrophin protein in the skeletal muscles and heart. The closely related disease Becker muscular dystrophy (BMD) is due to mutations in the dystrophin gene that result in dystrophin protein that's only partially functional.

Muscle satellite cells are required for the growth and repair of skeletal muscles. In previous studies, Rudnicki and his colleagues have found that there is a subset of muscle satellite cells that function as "satellite stem cells," giving rise to the satellite cells that then become muscle.

They've also found that satellite stem cells do not function properly in dystrophin-deficient mice; and that a protein called WNT7a stimulates proliferation of satellite stem cells and benefits normal and dystrophic muscle.

In this new set of experiments, Rudnicki's team will investigate the nature of the defect in satellite stem cells in dystrophin-deficient mice and the mechanism through which WNT7a treatment increases the numbers of these cells.

The researchers also will investigate the possibility of using WNT7a as a treatment for DMD or BMD, through experiments in dystrophin-deficient mice.

Rudnicki, who has received MDA support for several years, says, "MDA funding has been critical in allowing my lab to investigate the fundamental mechanisms that regulate the function of muscle stem cells."

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $447,092 over three years to Alessandra Sacco, an assistant professor in the Muscle Development and Regeneration Program at Sanford-Burnham Medical Research Institute in La Jolla, Calif. The grant will help support Sacco's research on early-stage transplantation of muscle stem cells to treat a mouse model of Duchenne muscular dystrophy (DMD).

The goal of Sacco's new study is to understand whether transplanting muscle stem cells into a DMD mouse model during the fetal or newborn period can prevent the muscle degenerative process seen in DMD.

Sacco said that, by the time DMD is diagnosed and treatment begins in children with the disease, significant damage to muscles has accumulated, which "poses a major hurdle to the design of efficient therapeutic approaches."

She said transplantation of muscle stem cells during fetal or neonatal life may enhance the regenerative potential of skeletal muscles, resulting in an improved therapeutic outcome.

Sacco's group will make use of a recently developed DMD mouse model, in which the mice lack two proteins. Like people with DMD, they lack dystrophin, a muscle protein that's completely absent in this disease and only partially functional in people with the related Becker muscular dystrophy (BMD); and they also lack telomerase, a repair enzyme. These mice have a severe DMD-like disease.

If the transplantation approach is successful in these mice, it could have applications to human DMD, BMD and perhaps other forms of MD.

"MDA has been fundamental to my career development," Sacco said. "During my postdoctoral training, I received an MDA development grant for studying the contribution of bone-marrow-derived cells to skeletal-muscle regeneration. In the difficult funding climate of the last few years, the efforts of this organization to promote research in this field have been outstanding."

Funding for this MDA grant began August 1, 2011.

Melissa Spencer, professor of neurology and co-director of the Center for Duchenne Muscular Dystrophy at the University of California, Los Angeles, has been awarded an MDA grant totaling $501,493 over three years. The funds will help support Spencer's continuing studies of the role of a protein called osteopontin and of inflammatory processes in a mouse model of Duchenne muscular dystrophy (DMD).

DMD results from a nearly complete absence of the dystrophin protein in the skeletal muscles and heart. Becker muscular dystrophy (BMD), a closely related disease, results from a partially functional dystrophin protein. A large variety of mutations in the dystrophin gene give rise to DMD or BMD.

The osteopontin protein has been shown to play a role in promoting the entry of immune system cells into damaged, dystrophin-deficient muscle, which in turn results in scar-tissue formation (fibrosis).

The Spencer lab has received funding from MDA over the past decade. Spencer and her colleagues, particularly Irina Kramerova and Carrie Miceli, will now study how osteopontin regulates the muscle-invading immune system cells and the manner in which these cells cause fibrosis in mice with a DMD-like disease.

The investigators will use mouse models and cellular and immunological techniques to understand the processes involved. They also will use a specialized mouse that has been genetically engineered to allow for noninvasive imaging of muscles.

These studies will lay the foundation for development of drugs that target osteopontin in DMD or BMD, Spencer said.

"I credit MDA for enabling many of the successes my lab has achieved," she noted.

Funding for this MDA grant began August 1, 2011.

MDA has awarded a research grant totaling $362,760 over three years to Kathryn Wagner, an associate professor of neurology and neuroscience at the Johns Hopkins School of Medicine and director of the Center for Genetic Muscle Disorders at the Kennedy Krieger Institute, both in Baltimore.

The grant will help support Wagner's studies of how a muscle protein called myostatin regulates the fate of muscle stem cells. The studies may have particular application to Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophy (CMD), facioscapulohumeral muscular dystrophy (FSHD) and limb-girdle muscular dystrophy (LGMD).

In most muscular dystrophies, muscle regeneration becomes less effective over time, and muscle is replaced by fibrosis (scar tissue).

"The factors that govern the establishment of fibrosis are not well-understood," Wagner said. "However, myostatin, a regulator of muscle growth, is one important factor in the development of fibrosis. In the absence of myostatin, muscle regenerates more quickly and with less fibrosis."

Wagner's studies will determine whether one of the cells that's important for muscle regeneration, a muscle stem cell called a satellite cell, can become misdirected and contribute to fibrosis. "The studies will specifically evaluate whether myostatin is a cue that directs satellite cells away from forming new muscle and toward fibrosis," Wagner said.

She noted that, if this hypothesis is correct, then anti-myostatin therapies could have an important role to play in stimulating muscle regeneration and reducing muscle fibrosis in a variety of diseases.

Funding for this MDA grant began August 1, 2011.

MDA awarded a research grant totaling $284,778 over a period of three years to Eric Wagner, an assistant professor in the department of biochemistry and molecular biology at the University of Texas Health Science Center in Houston. The funds will help support Wagner’s investigations into the role of the DUX4 gene in facioscapulohumeral muscular dystrophy (FSH, or FSHD).

Recent findings implicate the DUX4 gene as a likely causative factor in FSHD and a potential target for molecular therapies. It was found that in people with the disease the normally silent DUX4 gene is inappropriately activated, causing major problems in the muscles.

Wagner and colleagues have developed a reporter system that will monitor their ability to inhibit and study DUX4 expression in normal and FSHD-affected cells.

“The system allows us to design and test inhibitory agents that can antagonize Dux4 expression, which is thought to be the causative agent in FSHD,” Wagner said.

“The value of MDA research funding cannot be underestimated in bringing this research together,” Wagner said. “The recent and critical findings that demonstrated the importance of DUX4’s role in FSHD was funded by MDA, and is what encouraged my lab team to work on this problem.”

Funding for this MDA grant began August 1, 2011.

MDA has awarded a development grant totaling $180,000 over a period of three years to Junping Xin, research associate at the Neuroscience Institute, Loyola University Medical Center in Chicago, and Edward Hines Jr. Veterans Administration Hospital in Hines, Ill. The funds will help support Xin’s research into the possible effects of immune system dysfunction in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).

In particular, Xin plans to study a specific type of immune system cell called the CD4+ T cell, which when dysregulated may lead to increased disease-related inflammation in people with ALS. It’s also known, however, that CD4+ T cells play an important role in supporting motor neuron survival.

Xin, and colleagues, plan to elucidate the mechanisms of the CD4+ T cell-mediated neuroprotection as well as the effects that result when the cells become dysfunctional.

A better understanding of both the normal and dysfunctional roles of CD4+ T cells should provide a better understanding of their possible use in new experimental therapies to treat ALS.

“MDA funding is critical to my being able to investigate these questions,” Xin said. “This grant funding will provide me with the chance to not only help people with ALS, but to develop an independent career in research medicine.”

Funding for this MDA grant began August 1, 2011.

Margaret Zacharin, an associate professor in the department of endocrinology and diabetes at Royal Children's Hospital in Parkville, Victoria, Australia, has been awarded an MDA research grant totaling $268,021 over two years. The award will help support a clinical trial of the drug zoledronic acid in children and adolescents with Duchenne muscular dystrophy (DMD).

Zoledronic acid is part of a class of medications known as bisphosphonates, which are used to prevent bone loss in osteoporosis and other bone conditions.

Children with DMD lose bone in part because of their underlying disease and in part because of the effects of corticosteroid medications. These are commonly used to prolong muscle function in DMD but have adverse effects on bone density.

"Bisphosphonates alter the course of corticosteroid-induced bone loss and largely prevent this complication in the adult population," Zacharin said. "It's more difficult to provide such evidence in a pediatric population." However, she noted, with newer techniques of calculation available, more accurate data can now be obtained.

"We aim to determine whether intravenous zoledronic acid plus vitamin D and calcium is better than vitamin D and calcium alone in increasing spinal bone density, reducing bone turnover and/or reducing fracture rate over two years in boys with Duchenne muscular dystrophy."

Zacharin will work closely with Craig Munns, an associate professor in the Department of Endocrinology at Children’s Hospital in Westmead, New South Wales, Australia, on this project.

She said results of the zoledronic-acid study may be used to develop a larger trial to assess fracture reduction in the DMD population and might ultimately be extended to other diseases, including other neuromuscular disorders.

MDA support, she said, "will allow us to undertake and complete this important study in a timely fashion."

Funding for this MDA grant began August 1, 2011.