Gary Armstrong, a senior post-doctoral researcher at Université de Montréal in Quebec, Canada, was awarded a development grant totaling $177,670 over three years to further understanding of the synaptic defects that occur in ALS (amyotrophic lateral sclerosis). Abnormalities arising at the neuromuscular junction occur early in animal models of the disease and very little is known about the role central synaptic defects play in disrupting neuronal communication with the muscular system. A greater understanding of these abnormalities will facilitate the development of the next generation of therapeutics that target early functional defects and slow or stop the progression of ALS.

Funding for this MDA development grant began Aug. 1, 2015.

Robert Baloh, associate professor-in-residence in the department of neurology at the University of California, Los Angeles, has been awarded an MDA research grant totaling $300,000 over three years to study the molecular mechanism of type 2A Charcot-Marie-Tooth disease (CMT) due to mutations in the Mitofusin 2 (MFN2) gene. Baloh has developed a new mouse model that he will use in his research to test whether gene therapy with a gene called MFN1 could serve as a therapeutic approach.

Funding for this MDA research grant began Aug. 1, 2015. 

CMRI Claire Gordon Duncan Chair in Genetics and Professor of Pediatrics Sanjay Bidichandani, at University of Oklahoma Health Sciences Center in Oklahoma City, was awarded an MDA research grant totaling $300,000 over three years to address clinically and scientifically important questions regarding the use of existing and novel HDAC inhibitors to increase levels of the frataxin protein in Friedreich’s ataxia (FA). Bidichandani and colleagues recently found that the mechanism of gene silencing in FA involves shutting off the FXN gene promoter, a region of the gene that typically controls when and how much a gene should be turned on. They are now working to identify therapeutic molecules that will effectively reverse FXN promoter silencing in FA, and to determine the precise mechanism by which promoter inactivation and reactivation occurs.

Funding for this MDA research grant began Aug. 1, 2015.

Robert Burgess, a professor at The Jackson Laboratory in Bar Harbor, Maine, has been awarded an MDA research grant totaling $300,000 over three years. Burgess and co-investigator Scott Harper, associate professor at Nationwide Children’s Hospital Center for Gene Therapy in Columbus, Ohio, will test an AAV gene therapy approach to specifically block the altered form of the GARS gene in a newly developed mouse model for type 2D Charcot-Marie-Tooth disease (CMT). Successful completion of these studies could lead to a new therapy for type 2D CMT and provide a proof of principle for this approach that may be applicable to other types of CMT.

Funding for this MDA research grant began Aug. 1, 2015.

Arthur Burghes, professor of biological chemistry and pharmacology, molecular genetics, and neurology at The Ohio State University Wexner Medical Center in Columbus, was awarded an MDA research grant totaling $188,613 over two years to refine how a genotype can be used to predict the severity of spinal muscular atrophy (SMA). Burghes will develop assays to test whether SMA patients have either intact or defective SMN2 genes, which serve as the backup for the SMN1 gene lost in SMA patients. Since the level of SMN2 determines the disease severity in SMA patients, these assays may be able to better predict how disease may progress in an individual.

Funding for this MDA research grant began Aug. 1, 2015.

Don Cleveland, distinguished professor and chair in the department of cellular and molecular medicine at the University of California, San Diego, in La Jolla, was awarded an MDA research grant totaling $300,000 over three years to elucidate the mechanisms of ALS (amyotrophic lateral sclerosis)caused by mutations in the Fused in Sarcoma (FUS) gene. Cleveland and colleagues will be using newly developed mouse models to investigate whether alterations in the FUS gene cause ALS by a loss of the normal function of the FUS protein or through adoption of a new, toxic function of the protein. A better appreciation of how FUS alterations cause motor neuron death will aid in determining what type of treatment approach may work best for this type of ALS.

Funding for this ALS research grant began Aug. 1, 2015. 

Colin Crist, an assistant professor in the department of human genetics at McGill University in Québec, Canada, was awarded an MDA research grant totaling $300,000 over three years to investigate a biological mechanism that determines whether skeletal muscle stem cells, which play an important role in muscle regeneration, self-renew or differentiate. Crist has identified inhibitors that control this functional “switch.” This work may inform muscular dystrophy therapy development.

 Funding for this MDA research grant began Aug. 1, 2015.

Peter Currie, professor of medicine at Monash University in Australia, was awarded an MDA research grant totaling $300,000 over three years to test two therapeutic strategies for laminin alpha-2 deficiency in a zebrafish model of congenital muscular dystrophy (CMD). The work will support or refute the hypothesis that muscle fiber detachment is the primary defect in laminin 2-deficient muscular dystrophies, and could prompt a paradigm shift for therapeutic strategies in these diseases.

Funding for this MDA research grant began Aug. 1, 2015.

Antoine de Morrée, a postdoctoral scholar at Palo Alto Veterans Institute for Research and Stanford University in Palo Alto, Calif., was awarded an MDA development grant totaling $180,000 over three years to test a way to stop muscles from making toxic DUX4 protein as a possible treatment for facioscapulohumeral muscular dystrophy (FSHD). The goals of de Morrée’s work are to understand how cells make stabile RNA messages, and to develop a way to destabilize RNA messages that allow cellular machinery to produce the DUX4 protein. These studies have the potential to lead to new treatments that will reduce the toxicity in the muscles of patients with FSHD.

Funding for this MDA development grant began Aug. 1, 2015.

Alan A. and Edith L. Wolff Professor of Developmental Biology Aaron DiAntonio at Washington University school of Medicine in St. Louis was awarded an MDA research grant totaling $300,000 over three years to identify novel targets to block nerve degeneration in Charcot-Marie-Tooth disease (CMT). DiAntonio will perform a genetic screen in fruit flies to identify genetic suppressors of nerve degeneration and then test these targets in human nerve cells in a dish. The resulting targets will be potential candidates for the treatment of peripheral neuropathy and other disorders in which motor axons are lost.

Funding for this MDA research grant began Aug. 1, 2015.

Constantin d’Ydewalle, a postdoctoral fellow at Johns Hopkins School of Medicine in Baltimore was awarded an MDA development grant totaling $180,000 over three years to test a gene therapy designed to increase levels of SMN protein in spinal muscular atrophy (SMA). The work, co-funded by the American Association of Neuromuscular & Electrodiagnostic Medicine Foundation for Research and Education (AANEM), may lead to the development of a new treatment that could be useful by itself or in combination with other therapies in development.

Funding for this MDA development grant began Aug. 1, 2015.

James Ervasti, professor in the department of biochemistry, molecular biology & biophysics at the University of Minnesota in Minneapolis, was awarded an MDA research grant totaling $300,000 over three years to develop methods of identifying non-invasive biomarkers that can be measured in all patients across the entire spectrum of Duchenne muscular dystrophy (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.

Funding for this MDA research grant began Aug. 1, 2015. 

Kevin Foust, assistant professor in the department of neuroscience at Ohio State University in Columbus, was awarded an MDA research grant totaling $293,378 over three years to investigate disruption of gut bacteria in spinal muscular atrophy (SMA). The gut microbiome is the collection of organisms that inhabit a healthy gastrointestinal (GI) tract. Dysbiosis, or changes in the gut microbiome, disrupts GI motility, nutrient uptake and lipid metabolism, creating a spiral that impacts patient health.  Foust will examine the microbiome in mouse models of SMA and determine the effects of antibiotics, probiotics and fecal transplants on the SMA mouse microbiome. This study may help guide patients in the use of probiotics or other measures in order to maintain normal gastrointestinal function and nutritional health.

Funding for this MDA research grant began Aug. 1, 2015.

Ronald Haller, professor of neurology and neurotherapeutics at University of Texas Southwestern Medical Center in Dallas, was awarded an MDA research grant totaling $300,000 over three years to identify the cause and possible effective treatment for the oxidative defect that accompanies blocked glycogen breakdown in McArdle disease (phosphorylase deficiency). Haller plans to assess levels of metabolites in humans before and after exercise to better characterize the metabolic profile of patients, and test whether small increases in key molecules can help and improve patients’ capacity for exercise.

Funding for this MDA research grant began Aug. 1, 2015. 

Criss Hartzell, professor of cell biology at Emory University School of Medicine in Atlanta, Ga., was awarded an MDA research grant to elucidate the mechanisms underlying type 2L limb-girdle muscular dystrophy (LGMD), caused by mutations in the ANO5 gene. Hartzell will examine the role the ANO5 protein plays in trafficking and fusion of cell membranes during muscle repair, and how mutations in this protein disrupt these functions. The work may uncover unique targets around which to base new therapeutic approaches.

Funding for this MDA research grant began Aug. 1, 2015.

Yetrib Hathout, associate professor in the department of integrative systems biology at Children’s National Medical Center in Washington, D.C., was awarded an MDA research grant totaling $300,000 over three years to develop a panel of molecular biomarkers, detectable in blood, for Duchenne muscular dystrophy (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.

Funding for this MDA research grant began Aug. 1, 2015.

Justin Ichida, assistant professor in the department of stem cell biology and regenerative medicine at the University of Southern California in Los Angeles, was awarded an MDA research grant to elucidate the mechanisms underlying ALS (amyotrophic lateral sclerosis) caused by mutations in the C9ORF72 gene. Ichida will investigate whether mutations in the C9ORF72 gene lead to a loss of the protein’s normal function or a gain of a toxic new function, and how this could affect motor neuron health in ALS. Knowledge gained from this research will help inform scientists about whether future therapy development should aim to increase the protein’s normal function or reduce toxic downstream effects of altered C9ORF72 protein.

Funding for this MDA research grant began Aug. 1, 2015.

Aikaterini Kontrogianni-Konstantopoulos, an associate professor in the department of biochemistry and molecular biology at the University of Maryland School of Medicine in Baltimore, was awarded an MDA research grant totaling $300,000 over three years to study how the Myosin Binding Protein-C family of proteins may regulate contractile function of skeletal muscle in distal muscular dystrophy (DD). Kontrogianni-Konstantopoulos’ work will shed light on how mutations in this protein lead to disease and may have clinical relevance not only for distal arthrogryposis, but also for other muscular dystrophies as well.

Funding for this MDA research grant began Aug. 1, 2015.

Michael Kyba, at the University of Minnesota in Minneapolis, was awarded an MDA research grant totaling $300,000 over three years to study the role of satellite cells in skeletal muscle regeneration. Kyba’s research to discover and study genes that regulate the regenerative potential of satellite cells will lead to a better understanding of skeletal muscle regeneration, with implications for our understanding of skeletal muscle regeneration in disease states and of the differences in muscle regenerative potential between individuals.

Funding for this MDA research grant began Aug. 1, 2015.

Donghoon Lee, a research associate professor in the department of radiology at the University of Washington in Seattle, was awarded an MDA research grant totaling $300,000 over three years to develop imaging biomarkers for Duchenne muscular dystrophy (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.

Funding for this MDA research grant began Aug. 1, 2015.

Angelo Lepore, assistant professor in the department of neuroscience in Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, was awarded an MDA research grant totaling $300,000 over three years to examine a new mechanism by which non-nerve cells called astrocytes contribute to motor neuron death in ALS (amyotrophic lateral sclerosis). Despite being primarily a motor neuron disorder, studies in ALS animal models and with patient tissues suggest that cellular abnormalities are not limited to motor neurons. In particular, astrocytes, which are non-neuronal cells with important functions in the central nervous system, play a key role in ALS progression. However, the mechanisms involved in astrocyte contribution to ALS pathogenesis remain largely not understood, thus hampering development of effective therapies for targeting this cell population and for treating this disease. An improved understanding of how astrocytes contribute to motor neuron death may lead to new therapeutic targets.

Funding for this MDA research grant began Aug. 1, 2015

Ricardo Maselli, a professor in the neurology department at the University of California Davis was awarded an MDA research grant totaling $300,000 over three years to test whether transplantation of stem cells engineered to secrete a needed protein could be a beneficial treatment strategy in congenital myasthenic syndromes (CMS). If studies in a mouse model are successful, testing could advance to patients. Promising results could steer the field to a new therapeutic strategy for CMS.

Funding for this MDA research grant began Aug. 1, 2015.

Diane Merry, associate professor at Thomas Jefferson University in Philadelphia, was awarded an MDA research grant totaling $300,000 over three years to identify therapeutic opportunities to promote normal androgen receptor function while preventing the toxic effects of polyglutamine expansion in spinal-bulbar muscular atrophy (SBMA). Working with GlaxoSmithKline, Merry will test small molecule compounds that activate an enzyme called SIRT1 in cell and mouse models of SBMA to determine their therapeutic potential.

Funding for this MDA research grant began Aug. 1, 2015.

Dada Pisconti, at the University of Liverpool, United Kingdom, was awarded an MDA research grant totaling $300,000 over three years to study how the environment established by fibrosis and inflammation affects the maintenance and regenerative properties of muscle stem cells in Duchenne muscular dystrophy (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.

Funding for this MDA research grant began Aug. 1, 2015.

Liza Pon, professor of pathology and cell biology at Columbia University in New York was awarded an MDA research grant totaling $300,000 over three years to study the underlying mechanisms at work in CHKB congenital muscular dystrophy (CMD). Pon also will test whether therapies that promote function of a protein known as the ryanodine receptor (RyR), which plays a critical role in contraction of skeletal and heart muscle, can promote muscle function or prevent muscle degeneration in a mouse model for CHKB CMD and in muscle cells taken from CHKB CMD patients.

Funding for this MDA research grant began Aug. 1, 2015.

Thomas Rando, at Palo Alto Veterans Institute for Research and Stanford University in California, was awarded an MDA research grant totaling $300,000 over three years to develop 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 Duchenne muscular dystrophy (DMD) and other muscular dystrophies.

Funding for this MDA research grant began Aug. 1, 2015.

Jeffrey Rothstein, professor of neurology and neuroscience at Johns Hopkins University School of Medicine in Baltimore, was awarded an MDA research grant totaling $300,000 over three years to elucidate the mechanisms underlying ALS (amyotrophic lateral sclerosis) caused by mutations in the C9ORF72 gene. Rothstein will use ALS patient-derived stem cells to investigate the role of nuclear dysfunction in ALS caused by C9ORF72 mutations. The work could uncover novel drug targets for ALS.

Funding for this MDA research grant began Aug. 1, 2015.

Montserrat Samso, assistant professor in the department of physiology at Virginia Commonwealth University in Richmond, was awarded an MDA research grant totaling $300,000 over three years to generate a crystal structure of the ryanodine receptor (RyR1), an intracellular calcium channel, at high resolution and in different conformational states, with and without disease-causing mutations, to allow a better understanding of its function and role in central core disease (CCD). Samso aims to increase the basic understanding of a receptor critical for normal muscle function and provide the basis for rational structure-based design of small molecules aimed at counteracting the CCD-causing mutations that destabilize it.

Funding for this MDA research grant began Aug. 1, 2015.

Rita Sattler, associate professor of neurobiology at Barrow Neurological Institute, Dignity Health – St. Joseph’s Hospital in Phoenix, was awarded an MDA research grant totaling $300,000 over three years to elucidate the mechanisms underlying ALS (amyotrophic lateral sclerosis) caused by mutations in the C9ORF72 gene. Sattler will use patient stem cells and new mouse models to investigate whether alterations in the C9ORF72 gene lead to changes in the fine structure of nerve cells, which could affect the transmission of information between nerves. The identification of these changes will give further insight into how C9ORF72 mutations cause ALS and whether therapies targeting these associated changes could be beneficial for patients.

Funding for this MDA research grant began Aug. 1, 2015.

Daniel Summers, a postdoctoral research scholar in the department of genetics at Washington University School of Medicine in St. Louis, was awarded an MDA development grant totaling $180,000 over three years to investigate how activation of a protein called SARM leads to the loss of metabolites that are essential for the health of peripheral nerves in Charcot-Marie-Tooth disease (CMT). Further knowledge of this pathway may highlight whether blocking SARM may be a novel therapeutic approach for CMT and other peripheral neuropathies.

Funding for this MDA development grant began Aug. 1, 2015.

Shinichi Takayama, a research associate professor at Boston University School of Medicine, was awarded an MDA grant totaling $300,000 over three years to identify potential therapeutic targets in limb-girdle muscular dystrophy (LGMD). Takayama will study the scaffolding protein BAG3 and its interactions with proteins implicated in myofibrillar myopathies and LGMD. This innovative approach could reveal that a group of diseases have a common pathogenesis caused by aberrant protein assembly and could point the way to future therapeutic strategies.

Funding for this MDA research grant began Aug. 1, 2015.

DeWayne Townsend, assistant professor at the University of Minnesota in Minneapolis, was awarded an MDA research grant totaling $300,000 over three years to study the role of oxygen in the Duchenne muscular dystrophy (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.

Funding for this MDA research grant began Aug. 1, 2015.

Davide Trotti, professor of neuroscience at Thomas Jefferson University in Philadelphia, was awarded an MDA research grant totaling $300,000 over three years to elucidate the mechanisms of ALS (amyotrophic lateral sclerosis) caused by mutations in the C9ORF72 gene. Trotti will study how the accumulation of protein clumps in patients with C9ORF72 ALS may contribute to motor neuron death. If these protein clumps are shown to drive the ALS disease process, drugs could be developed to block their accumulation or dissolve the clumps. 

Funding for this MDA research grant began Aug. 1, 2015.

Natassia Vieira, an investigator at Biosciences Institute, University of São Paulo - São Paulo, Brazil, was awarded an MDA development grant totaling $180,000 to study a genetic mechanism that appears to compensate for mutations in the gene that causes Duchenne muscular dystrophy (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 new drug target for DMD.

Funding for this MDA development grant began Aug. 1, 2015.

Rebecca Willcocks, an adjunct research assistant scientist in the department of physical therapy at the University of Florida in Gainesville, has been awarded an MDA development grant totaling $171,422 over three years to study magnetic resonance biomarkers in Duchenne muscular dystrophy (DMD). Willcocks will use 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.

 Funding for this MDA development grant began Aug. 1, 2015.

Haining Zhu, a professor in the department of molecular and cellular biochemistry at the University of Kentucky in Lexington, was awarded an MDA research grant totaling $300,000 over three years to study the underlying mechanisms of ALS (amyotrophic lateral sclerosis) caused by mutations in the Fused in Sarcoma (FUS) gene. Zhu recently has found that the FUS protein in ALS is modified by the addition of a phosphate group — a process called phosphorylation. He’s now working to understand what role phosphorylation of the FUS protein plays in causing the protein to become toxic and whether use of an inhibitor to block phosphorylation can prevent toxicity and normalize FUS function. If successful, Zhu’s work could lead to a new therapeutic strategy for ALS.

Funding for this MDA research grant began Aug. 1, 2015.