Douglas Anderson, a postdoctoral fellow at the University of Texas Southwestern Medical Center at Dallas, was awarded an MDA development grant totaling $180,000 over three years to study a regulator of muscle performance called myoregulin and its role in muscle disease, including congenital muscular dystrophy (CMD). Anderson will investigate how an excess of myoregulin induces a muscular dystrophy-like condition in mice and will explore the potential to target myoregulin as a therapeutic strategy in muscle disease.

Funding for this MDA research grant began Feb. 1, 2016.

Paul August, at Sanofi, was awarded an MDA research grant totaling $298,500 over a period of three years to develop a neuron-muscle contraction unit on a chip. On the chip, developed using cells derived from people with amyotrophic lateral sclerosis (ALS), motor neurons will cause muscle cells to contract. The development of this innovative tool provides for a complete muscle-nerve unit, which could be used to test drugs and better understand the mechanisms behind motor neuron death in ALS. 

Funding for this MDA research grant began Feb. 1, 2016.

Antoni Barrientos, professor of neurology and of biochemistry and molecular biology at the University of Miami Miller School of Medicine in Miami, Fla., was awarded an MDA research grant totaling $300,000 over a period of three years to address a knowledge gap about mitochondrial protein complex assembly defects, which are a frequent cause of inherited mitochondrial myopathies. This project will not only improve our understanding of a process fundamentally central to mitochondrial processing, but also explore interventions that improve functioning and disease phenotypes.

Funding for this MDA research grant began Feb. 1, 2016.

Asim Beg, assistant professor at University of Michigan in Ann Arbor, was awarded an MDA research grant totaling $300,000 over a period of three years to study the role of a protein, EphA4, in amyotrophic lateral sclerosis (ALS). High levels of EphA4 correlate with rapid disease progression in ALS patients. Beg and colleagues will work on the development of a strategy to reduce EphA4 levels. This work will provide insight into the molecular mechanisms of motor neuron degeneration and will facilitate new strategies to slow ALS disease onset and progression.

Funding for this MDA research grant began Feb. 1, 2016.

Alan Beggs, professor of pediatrics at Children’s Hospital Boston, was awarded an MDA research grant totaling $300,000 over a period of three years to uncover new genes that cause nemaline myopathy in patients and families where the underlying cause has not yet been identified. To better understand the biological pathways that lead to disease and to aid the search for effective therapies, Beggs will then develop zebrafish, mouse and dog models containing the newly uncovered mutations.

Funding for this MDA research grant began Feb. 1, 2016.

Steve Cannon, professor of physiology at the David Geffen School of Medicine at the University of California, Los Angeles, was awarded an MDA research grant totaling $300,000 over three years to investigate a new hypothesis about the underlying mechanisms involved in periodic paralysis. New preliminary studies in research models have revealed a profound loss of muscle force within minutes of recovery from exposure to high carbon dioxide levels, which Cannon and colleagues suggest may be a surrogate for the exercise-induced attacks of weakness that occurs in patients. Cannon and his team will investigate the mechanistic basis for exercise-induced weakness in periodic paralysis, will strategically select drugs that may block this process, and will test the potential of these drugs to foreshorten or prevent attacks of periodic paralysis.

Funding for this MDA research grant began Feb. 1, 2016.

Matthew Disney, a professor at the Scripps Research Institute in Jupiter, Fla., was awarded an MDA research grant totaling $300,000 over a period of three years to optimize two novel, drug-like compounds — one that targets toxic RNA in myotonic muscular dystrophy and another that targets toxic RNA in amyotrophic lateral sclerosis (ALS). Using innovative methods they have developed, Disney and colleagues will study the compounds in patient-derived cells and mouse models to identify any off-target effects, which could cause side effects. This work could accelerate treatments for myotonic muscular dystrophy and ALS.

Funding for this MDA research grant began Feb. 1, 2016.

James Dowling, a clinician-scientist in the department of pediatrics at The Hospital for Sick Children in Toronto, Canada, was awarded an MDA research grant totaling $300,000 over three years to build a central core disease (CCD) drug development platform. This new drug development tool will include high throughput screening in zebrafish models and final testing in patient-derived myotubes. The platform is expected to help identify drugs suitable for translation to patients with CCD and other myopathies stemming from type 1 ryanodine receptor (RyR1) defects.

Funding for this MDA research grant began Feb. 1, 2016.

Pradeep Reddy Dubbaka Venu, a research associate at the Salk Institute for Biological Studies, La Jolla, Calif., was awarded an MDA development grant totaling $180,000 over a period of three years to test a potential method for preventing transmission of mitochondrial myopathies by selective elimination of defective mitochondrial DNA in oocytes (immature egg cells). The approach involves using enzymes called nucleases to act as “molecular scissors” that are able to precisely enter mitochondria and specifically identify and eliminate mutated mitochondrial DNA. The feasibility of the approach has been demonstrated in mouse embryos, where it successfully prevented the transmission of targeted mitochondrial DNA to the next generation. Dubbaka Venu and colleagues will test the safety and efficacy of the approach in human oocytes from mitochondrial disease patients. If successful, this work could lead to the first-in-history correction of genetic diseases at the oocyte level and the potential eradication of mitochondrial diseases.   

Funding for this MDA research grant began Feb. 1, 2016.

Mahasweta Girgenrath, an assistant professor at Boston University in Massachusetts, was awarded an MDA research grant totaling $200,000 over a period of two years to test the translational potential of pairing two different therapies in one of the most prevalent forms of congenital muscular dystrophy (CMD). This work will identify an optimal time window when a dual therapy will be most effective in a mouse model of MDC1A, and could inform progress towards the design of similar trials in humans. 

Funding for this MDA research grant began Feb. 1, 2016.

Susan Hamilton, L.F. McCollum Chair in Molecular Physiology at Baylor College of Medicine in Houston, was awarded an MDA research grant totaling $300,000 over three years to further define the molecular mechanisms underlying central core disease (CCD) and develop new treatments. Hamilton will test three different types of therapeutic interventions in two mouse models of CCD. Since the two mouse models demonstrate different ways that mutations in the ryanodine receptor (RyR1) can lead to dysfunction, and the three drugs are already approved for use or currently in clinical trials for other diseases, these studies could lay the ground work for rapid development of therapies in CCD.

Funding for this MDA research grant began Feb. 1, 2016.

Claudio Hetz, a professor in the Faculty of Medicine at the University of Chile, was awarded an MDA research grant totaling $294,000 over a period of three years to study a potential new therapy aimed at rescuing motor neurons in amyotrophic lateral sclerosis (ALS). In ALS, some proteins do not fold into their required shape correctly, triggering stress-response pathways which can be detrimental to neurons. Hetz aims to use a gene therapy approach to target one of these stress response pathways, known as the “Unfolded Protein Response” (UPR). If successful, the work could point the way to a new therapeutic target at which to aim treatments for this fatal disease. 

Funding for this MDA research grant began Feb. 1, 2016.

Henry Houlden, professor of neurology at the MRC Centre for Neuromuscular Diseases, University College London Institute of Neurology in England, was awarded an MDA research grant totaling $288,151 over three years to elucidate the genetic causes of severe forms of Charcot-Marie-Tooth disease (CMT) and other types of early-onset neuropathy. Identification of the causative genes could help optimize treatment strategies and accelerate new therapy development.

Funding for this MDA research grant began Feb. 1, 2016.

Peter Jones, associate professor in cell and developmental biology and neurology at University of Massachusetts Medical School in Worcester, was awarded a research grant totaling $300,000 over a period of three years to develop a research mouse model for facioscapulohumeral muscular dystrophy (FSHD). A major obstacle to FSHD drug development has been the absence of a mouse model that effectively recapitulates the human disease symptoms. Jones and colleagues have engineered a mouse model that contains the human DUX4 gene, based on the widely accepted understanding that FSHD is caused by increased expression of the gene. Now the team will work to develop different versions of the mouse to represent various levels of human FSHD disease severity. Successful completion of the project will provide the FSHD field with valuable tools for understanding what happens in the disease and for preclinical screening of different classes of potential therapies aimed at DUX4 and downstream targets.

Funding for this MDA research grant began Feb. 1, 2016.

Nam Chul Kim, a postdoctoral associate at St. Jude Children’s Research Hospital in Memphis, was awarded an MDA development grant totaling $180,000 over a period of three years to study the disease-causing mechanism in amyotrophic lateral sclerosis (ALS) caused by mutations in the VCP gene. Kim will investigate the abnormal interaction between VCP protein and another protein called UBE4B and test whether inhibiting the interaction between the two proteins could be a useful therapeutic strategy.

Funding for this MDA research grant began Feb. 1, 2016.

Evangelos Kiskinis, assistant professor in the department of neurology & physiology at Feinberg School of Medicine, Northwestern School of Medicine in Chicago, was awarded an MDA research grant totaling $300,000 over three years to decipher the degree of mechanistic overlap in different forms of amyotrophic lateral sclerosis (ALS). Using cutting-edge technology, Kiskinis will activate ALS patient motor neurons in culture by shining a light on them to cause them to fire. Motor neurons from people with different forms of the disease will be examined to determine if their firing patterns are similar or divergent. Results from this work may yield insight into whether certain drugs will be broadly relevant to all ALS patients or, instead, work better for specific subgroups of patients. 

Funding for this MDA research grant began Feb. 1, 2016.

Louis Kunkel, professor of genetics and pediatrics at Children’s Hospital in Boston, was awarded an MDA research grant totaling $300,000 over a period of three years to identify genetic modifiers in facioscapulohumeral muscular dystrophy (FSHD). Disease severity among patients with FSHD varies widely, and may reflect the various contributions of genetic modifiers — genes that minimize or exacerbate symptoms. To identify genetic modifiers, Kunkel will screen the human genome, then validate hits both by cross-referencing with patient data and by determining effects in a zebrafish research model.

Funding for this MDA research grant began Feb. 1, 2016.

Gabsang Lee, assistant professor in the department of neurology at Johns Hopkins University in Baltimore, was awarded an MDA research grant totaling $300,000 over a period of three years to create a human cellular model of Duchenne muscular dystrophy (DMD). Using stem cells derived from blood, he will generate patient-specific muscle cells, confirm that the cells accurately reflect the disease, and validate the utility of the cells using drug screening and gene knockout. Such a “DMD-in-a-dish” model could facilitate fast and accurate testing of investigational therapies.

Funding for this MDA research grant began Feb. 1, 2016.

Monkol Lek, senior research fellow at Massachusetts General Hospital in Boston, was awarded an MDA development grant totaling $119,746 over a period of two years to increase the diagnosis rate for limb-girdle muscular dystrophy (LGMD) through whole-genome sequencing. The work, co-funded by the American Association of Neuromuscular & Electrodiagnostic Medicine Foundation for Research and Education (AANEM), is expected to lead to the identification of novel neuromuscular disease genes, which will provide deeper understanding of common disease mechanisms. Future treatment development can then be prioritized to target common mechanisms in order to benefit a larger number of patients.

Funding for this MDA research grant began Feb. 1, 2016.

Chris Lorson, professor of veterinary pathology, and molecular biology and immunology at the University of Missouri in Columbia, was awarded an MDA research grant totaling $300,000 over a period of three years to optimize an approach currently in clinical trials for spinal muscular atrophy (SMA) by delivering an enhanced form of drug combined with other potential synergistic therapies. This work could provide evidence for an innovative combinatorial approach to SMA that would address a broad range of patient needs.

Funding for this MDA research grant began Feb. 1, 2016.

Ke Ma, an assistant professor at Houston Methodist Research Institute in Texas, was awarded an MDA research grant totaling $300,000 over a period of three years to investigate whether a new drug improves the repair ability of skeletal muscle and test its potential as a new therapy for Duchenne muscular dystrophy (DMD). Ma and colleagues will study how the drug promotes muscle stem cell functions to improve repair of diseased muscle and its function. They also will determine the mechanisms mediating the effects of this molecule and its molecular targets in a research mouse model. The outcomes from the studies will determine potential future applications of this new agent as a treatment for muscular dystrophy.

Funding for this MDA research grant began Feb. 1, 2016.

Jim Manley, JC Levi Professor of Life Sciences at Columbia University in New York, was awarded an MDA research grant totaling $299,445 over three years to study what goes wrong in ALS4, a form of amyotrophic lateral sclerosis (ALS) that begins in childhood or adolescence and is caused by mutations in the gene that encodes for the senataxin protein. Manley aims to investigate how the absence of senataxin protein affects autophagy, a cellular process that clears unwanted and defective components of cells and which, when disrupted, can lead to cell toxicity and ultimately cell death. Further knowledge of how this pathway is affected in ALS4 may inform the development of a targeted, therapeutic approach for this type of ALS and potentially other subtypes of the disease as well.

Funding for this MDA research grant began Feb. 1, 2016.

Steven Markus, assistant professor at Colorado State University in Fort Collins, Colo., was awarded an MDA research grant totaling $300,000 over a period of three years to study alterations in the dynein gene and their effects in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Alterations in the dynein gene disrupt the transportation highway in the cell responsible for delivering cargo to appropriate locations to promote cell growth, maintenance and division. Defects in this process compromise the survival and maintenance of several cell types, most notably motor neurons that communicate information from the spinal cord to muscles throughout the body. Markus’ work to elucidate the molecular basis for dynein dysfunction in motor neuron disease could lay the foundation to identify effective, targeted therapies.

Funding for this MDA research grant began Feb. 1, 2016.

Kathrin Meyer, a postdoctoral researcher at Nationwide Children’s Hospital in Columbus, Ohio, was awarded an MDA development grant totaling $180,000 over three years to study the roles of cell types other than motor neurons in amyotrophic lateral sclerosis (ALS). Meyer will use new reprogramming techniques to generate cell types found in the central nervous system from patient skin biopsies and study them in a culture dish. In addition to increasing our understanding of the role these cells play in ALS, the model system may be used to compare cells from different patients in order to find properties associated with a slow or fast disease progression. Meyer’s work could lead to better methods in predicting patient clinical outcomes and grouping patients in clinical trials to maximize the potential for success.

Funding for this MDA research grant began Feb. 1, 2016.

Michael Miller, professor at the University of Alabama at Birmingham, was awarded an MDA research grant totaling $300,000 over three years to study underlying mechanisms in amyotrophic lateral sclerosis (ALS) caused by mutations in the VAPB gene. In studies conducted in worms, flies, mice and humans, Miller and colleagues have demonstrated that VAPB protein is a circulating factor (found in blood and spinal fluid), which plays an important role in motor neuron and skeletal muscle energy metabolism. Miller’s work aims to increase understanding about whether low blood levels of the VAPB protein can predispose individuals to develop ALS. In addition, the results of his studies could lead to the use of VAPB protein as a biomarker for ALS and inform methods to increase VAPB levels as a potential therapy for patients.

Funding for this MDA research grant began Feb. 1, 2016.

Bradley Olwin, a professor at the University of Colorado, Boulder, was awarded an MDA research grant totaling $300,000 over a period of three years to investigate the role satellite cells play in muscle repair in Duchenne muscular dystrophy (DMD). Current dogma states that repair of dystrophic muscle eventually fails due to depletion of satellite cells. Olwin has reported evidence of another possiblity: impaired activation (not loss) of these satellite cells may slow repair. Olwin will investigate whether satellite cell activation can be stimulated by the deletion of syndecan-3, and whether such stimulation promotes muscle repair. Further, he will determine whether it will improve repair in mouse models of congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD).

Funding for this MDA research grant began Feb. 1, 2016.

Franco Pagani, at the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, was awarded an MDA research grant totaling $224,950 over a period of three years to investigate a new therapeutic strategy for spinal muscular atrophy (SMA). Pagani will study a small RNA molecule called Exon Specific U1 (ExSpeU1), which may be able to correct the splicing defect in the SMN2 gene, resulting in restored SMN protein levels. His work could result in a therapy that will achieve higher SMN protein levels than drugs currently in clinical trials for SMA.

Funding for this MDA research grant began Feb. 1, 2016.

Alex Parker, associate professor at the University of Montreal CHUM Research Center in Montreal, Quebec (Canada), was awarded an MDA research grant totaling $295,470 over a period of three years to study disease mechanisms and identify new therapeutic approaches in amyotrophic lateral sclerosis (ALS). Using an ALS worm model, Parker and colleagues discovered an immune system pathway that is inappropriately activated in ALS, contributing to cell death. Now he and his team will work to determine whether this inappropriate activation spans across multiple types of ALS, in addition to testing drugs to modify the pathway, potentially leading to new therapies for ALS patients.

Funding for this MDA research grant began Feb. 1, 2016.

Livio Pellizzoni, associate professor at Columbia University Medical Center in New York, was awarded an MDA research grant totaling $200,000 over two years to elucidate the underlying mechanisms of spinal muscular atrophy (SMA). Although several strategies to restore SMN levels have shown promising results in preclinical studies and are currently being tested in clinical trials, it remains essential to understand the still elusive mechanisms by which low SMN causes SMA and to define other therapeutic targets that can be pursued in parallel to SMN-enhancing approaches. To address these issues, Pellizzoni will determine whether disruption of a novel function of SMN in RNA regulation contributes to SMA pathology in a well-established mouse model that recapitulates many features of the human disorder. This work has the potential to identify new research avenues for the development of therapeutic approaches that could complement current strategies for upregulation of SMN.

Funding for this MDA research grant began Feb. 1, 2016.

Thomas Philips, a postdoctoral researcher at Johns Hopkins University School of Medicine in Baltimore, was awarded an MDA development grant totaling $180,000 over a period of three years to validate a new drug target for amyotrophic lateral sclerosis (ALS). Philips will study monocarboxylate transporter 1 (MCT1), which mediates transport of essential nutrients from oligodendrocytes (neural support cells) to motor neurons and has been found to be dysregulated in ALS. An enhanced understanding of the role MCT1 transporters play in disease could pave the way to therapeutic interventions designed to restore metabolic support to motor neurons.

Funding for this MDA research grant began Feb. 1, 2016.

Natalia Rodriguez Muela, a postdoctoral fellow at Harvard University in Cambridge, Mass., was awarded an MDA development grant totaling $179,985 over a period of three years to deepen our understanding of what goes wrong in spinal muscular atrophy (SMA), a progressive disease caused by low levels of SMN protein. The work will focus on how the SMN protein is degraded in the cell in SMA. If the degradation pathway can be blocked, it could point to a potentially new, exciting approach to treat SMA.

Funding for this MDA research grant began Feb. 1, 2016.

Michael Rudnicki, a professor at Ottawa Hospital Research Institute in Ontario, Canada, was awarded an MDA research grant totaling $300,000 over a period of three years to develop Wnt7a as a protein biologic for the treatment of Duchenne muscular dystrophy (DMD). Wnt7a increases satellite cell number and activity, thereby promoting repair in muscle. To test whether Wnt7a could serve as an effective therapy, Rudnicki will examine the effects of Wnt7a treatment on satellite cell expansion and muscle repair in a mouse model of DMD.

Funding for this MDA research grant began Feb. 1, 2016.

Alessandra Sacco, an associate professor at Sanford Burnham Prebys Medical Discovery Institute in San Diego, was awarded an MDA research grant totaling $297,837 over a period of three years to study the role the diseased microenvironment has on muscle stem cell function in Duchenne muscular dystrophy (DMD). Sacco and colleagues will modulate the sensitivity of muscle stem cells to the environment, and determine whether it promotes their effective expansion in dystrophic muscle, thus restoring their ability to repair damaged tissue and delay disease progression. This work will improve understanding of the progressive decline in tissue maintenance in DMD and inform the development of strategies to ameliorate DMD symptoms.

Funding for this MDA research grant began Feb. 1, 2016.

Melissa Spencer, professor of neurology at the Regents of the University of California, Los Angeles, was awarded an MDA research grant totaling $450,988 over a period of three years to work with PTC Therapeutics on the development of a treatment for Duchenne muscular dystrophy (DMD). Expression of serum protein osteopontin is abnormally high in DMD patients and has been implicated in driving functional decline and increased fibrosis. In collaboration with PTC Therapeutics, Spencer aims to develop and test osteopontin inhibitors to block fibrosis and slow disease progression. This work will identify the best drug candidate among PTC Therapeutics’ lead compounds and will optimize its dosing regimen.

Funding for this MDA research grant began Feb. 1, 2016.

Kim Staats, a postdoctoral researcher at the University of Southern California in Los Angeles, was awarded an MDA development grant totaling $180,000 over a period of three years to study potential causes for sporadic amyotrophic lateral sclerosis (ALS). Using a cutting-edge approach to identify genetic contributors in sporadic ALS, Staats has found a new gene called SEC14L5 with ties to C9ORF72, the most common cause of familial ALS. Now she will elucidate the role of an identified SEC14L5 mutation in motor neuron death in ALS, increasing understanding of ALS disease mechanisms and facilitating the development of therapeutic strategies. 

Funding for this MDA research grant began Feb. 1, 2016.

Tamar Sztal, a postdoctoral fellow at the School of Biological Sciences, Monash University, in Melbourne, Australia, was awarded an MDA development grant totaling $180,000 over a period of three years to screen more than 1,200 FDA-approved drugs in a zebrafish model of nemaline myopathy to determine which are most effective at increasing muscle function and reducing disease severity.

Funding for this MDA research grant began Feb. 1, 2016.

Christine Vande Velde, associate professor at the University of Montreal CHUM Research Center in Montreal, Quebec (Canada), was awarded an MDA research grant totaling $300,000 over a period of three years to study what goes wrong in amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene. In ALS patients with SOD1 genetic mutations, the SOD1 protein does not adopt the correct shape, leading to its abnormal interaction with cellular energy factories known as mitochondria. Vande Velde will examine how this interaction occurs, with the future goal of blocking this inappropriate interaction as a potential ALS therapy.

Funding for this MDA research grant began Feb. 1, 2016.