Grant - Spring 2014 - DMD - Darek Gorecki, Ph.D.
Darek Gorecki, a professor of molecular medicine at the University of Portsmouth in the United Kingdom, has been awarded an MDA research grant totaling $253,800 over three years to study whether blocking a specific receptor (molecular docking site) that enhances inflammation can be beneficial to muscle fibers affected by Duchenne muscular dystrophy (DMD). He will conduct experiments in mice.
Funding for this MDA research grant began May 1, 2014.
Grantee: DMD - Darek Gorecki, Ph.D.
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Grant - Spring 2014 - DMD - Da-Zhi Wang, Ph.D.
Da-Zhi Wang, an associate professor of pediatrics at Boston Children's Hospital and Harvard Medical School, was awarded an MDA research grant totaling $253,800 over three years to study the role of a compound called miR-155, a "microRNA," in muscle function and regeneration and to see whether reducing it could help treat Duchenne muscular dystrophy (DMD). Wang has found that mice with lacking miR-155 have better muscle function and regeneration than mice that have this substance. He and his colleagues will study mice with a disorder resembling human muscular dystrophy to define the function of miR-155, with an eye to therapy development targeting this compound.
Funding for this MDA research grant began May 1, 2014.
Grantee: DMD - Da-Zhi Wang, Ph.D.
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Grant - Spring 2014 - CMT/DSD - Kelly Monk, Ph.D.
Kelly Monk, an assistant professor of developmental biology at Washington University in St. Louis, was awarded an MDA research grant totaling $253,800 over three years to investigate a possible therapeutic avenue for treating Charcot-Marie-Tooth disease (CMT) and the related Dejerine-Sottas disease (DSD). Monk and her colleagues have previously found that a protein called GPR126 is required for proper formation and maintenance of the myelin sheath that insulates fibers in the peripheral nervous system, and they will now study how this protein controls this process, which is known as myelination. They will also look at the role of a related protein called GPR56 and will investigate whether either or both of these proteins could represent new drug development targets for CMT or DSD.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT/DSD - Kelly Monk, Ph.D.
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Grant - Summer 2013 - DMD — Hansell Stedman, M.D.
Hansell Stedman, associate professor of surgery at the University of Pennsylvania in Philadelphia, was awarded an MDA research grant totaling $300,000 over a period of three years to study early immune responses during administration of gene therapy.
Gene therapy is a promising treatment strategy for Duchenne muscular dystrophy (DMD) and other muscle diseases, but it has been hindered by the body’s immune response. Genes can be delivered via virus-like particles (viral vectors), but the immune system can identify them as foreign, and mount a response that can inactivate the vector and cause inflammation in the muscle. Stedman plans to study the very earliest phases of the immune response, combining approaches gleaned from immunology, surgical critical care, genetics and virology.
“This mechanistic information will identify rational targets for transient immunosuppression prior to vector administration,” Stedman says, “thereby improving the chances for safe and durable therapy for these devastating childhood-onset diseases.” His work will be performed in the mouse model of DMD.
“In our view, the entire field is tantalizingly close to the development of gene therapy for Duchenne and other forms of muscular dystrophy, but we must explore a number of strategies to address the remaining obstacles,” he says. “Understanding how the innate immune system recognizes injured cells should improve our chances for a successful intervention.”
Funding for this MDA grant began August 1, 2013.
Grantee: DMD — Hansell Stedman, M.D.
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Grant - Winter 2012 - ALS - Terry Heiman-Patterson, M.D.
MDA awarded a research grant totaling $330,000 over a period of three years to Terry Heiman-Patterson, section chief of neuromuscular disorders at Drexel University College of Medicine in Philadelphia. Heiman-Patterson also is medical director of the MDA/ALS Center of Hope at that institution.
The newly awarded funds will help support Heiman-Patterson's work to identify "modifier" genes in mouse models of amyotrophic lateral sclerosis (ALS).
A great deal is known about one of the most commonly used mouse models of ALS — the SOD1 mouse. This model carries mutations in the SOD1 gene and develops some of the same signs and symptoms exhibited by people with SOD1-related ALS.
"Our lab, along with others, have shown that disease severity in these transgenic mice depends on their genetic background," Heiman-Patterson said.
With colleagues, Heiman-Patterson plans to compare a number of mouse models and identify genes that are able to modify disease.
It's already suspected that a region on chromosome 17 modifies disease severity in mice with certain backgrounds. Heiman-Patterson's team intends to validate that the region of chromosome 17 does modify disease, to identify the responsible gene within the region, and to test whether the gene also can affect severity in other models of motor neuron disease.
The identification of modifier genes will provide new targets for therapy development.
Grantee: ALS - Terry Heiman-Patterson, M.D.
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Grant - Winter 2012 - ALS - Kenneth Hensley, Ph.D.
MDA awarded a research grant totaling $328,153 over a period of three years to Kenneth Hensley, associate professor in the departments of pathology and neuroscience, and research director in the department of pathology at the University of Toledo Medical Center in Ohio. The funds will help support Hensley’s study of a potential new target and treatment strategy for amyotrophic lateral sclerosis (ALS).
Recent findings from Hensley’s laboratory and from other groups, Hensley said, suggest that ALS actually begins near the junction of nerve and muscle (the neuromuscular junction, or NMJ).
“We hypothesize that molecules called semaphorins acting inappropriately near the NMJ signal axons, the long fibers that extend and carry information away from the bodies of motor neurons (nerve cells). The semaphorins’ signals cause the axons to move away from the muscle and ‘collapse’ backward toward the spinal cord.”
Research conducted by Hensley and colleagues implicates a protein calledcollapsing response mediator protein-2, or CRMP2, in this process of axon degeneration. The group will now test three distinct pharmacological (drug-based) approaches to interrupting CRMP2-dependent axon degeneration in the SOD1 research mouse model of ALS.
“We have invented and patented small molecule compounds calledlanthionines that bind CRMP2 and inhibit or reverse CRMP2-dependent axonal degeneration,” Hensley said.
The investigators also are researching antibodies that could be administered to people with ALS, where they would block semaphorin binding to neural receptors and prevent the inappropriate activation of CRMP2 pathways.
Grantee: ALS - Kenneth Hensley, Ph.D.
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Grant - Spring 2014 - CMT - Nivedita Jerath, M.D.
Nivedita Jerath, a clinical fellow in neuromuscular medicine at the University of Iowa, has been awarded an MDA clinical research training grant to study driving ability in patients with the type 1A form of Charcot-Marie-Tooth disease (CMT). Because of difficulties with strength and balance, as well as foot abnormalities and tight ankles, the disease may affect driving, which requires quick responses, such as slamming on the brakes or turning the steering wheel quickly. Using a driving simulator as well as a special car that can videotape driver performance on the road, Jerath will investigate whether or not patients with CMT1A can drive normally. If they are found to have driving difficulties, Jerath says, she hopes the findings can be used to develop devices that might help people with CMT1A to drive more safely.
Funding for this MDA grant began July 1, 2014
Grantee: CMT - Nivedita Jerath, M.D.
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Grant - Winter 2012 - ALS - Eric Huang, M.D., Ph.D.
MDA awarded a grant totaling $412,500 over a period of three years to Eric Huang, professor of neuropathology at the University of California in San Francisco. The funds will help support Huang’s work to create cellular and mouse models of amyotrophic lateral sclerosis (ALS) that is caused by mutations in the fused in sarcoma (FUS) gene.
Genetic data have shown that mutations in the FUS gene can be identified in more than 5 percent of people with familial (inherited) ALS.
Huang and colleagues hypothesize that these FUS mutations interfere with the normal production of proteins, ultimately leading to the degeneration and death of the nerve cells called motor neurons.
The team’s goal is to create cellular and transgenic mouse models of FUS-related ALS that can be used to determine the ways in which mutant FUS proteins cause motor neuron degeneration.
Studies in the new FUS transgenic mice are expected to provide novel insights into the disease process and therapeutic targets for ALS, Huang said.
Grantee: ALS - Eric Huang, M.D., Ph.D.
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Grant - Spring 2014 - CMT - Michael Shy, M.D.
Michael Shy, a professor of neurology and pediatrics at the University of Iowa, has been awarded an MDA research grant totaling $253,800 over three years to develop a clinical trial to test a treatment for patients with the type 1B form of Charcot-Marie-Tooth disease (CMT). Based on previous MDA-supported work in mice with a CMT1B-like disorder, Shy and colleagues believe that treating a cellular phenomenon called the ER stress response may help CMT1B patients.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT - Michael Shy, M.D.
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Grant - Spring 2014 - CMT - Michael Shy, M.D.
Michael Shy, a professor of neurology and pediatrics at the University of Iowa, has been awarded an MDA research grant totaling $253,800 over three years to develop a clinical trial to test a treatment for patients with the type 1B form of Charcot-Marie-Tooth disease (CMT). Based on previous MDA-supported work in mice with a CMT1B-like disorder, Shy and colleagues believe that treating a cellular phenomenon called the ER stress response may help CMT1B patients.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT - Michael Shy, M.D.
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Grant - Winter 2012 - ALS - Claudio Hetz, Ph.D.
Claudio Hetz, full professor at the Institute of Biomedical Sciences, Faculty of Medicine at the University of Chile in Santiago, was awarded an MDA research grant totaling $217,500 over a period of three years. The funds will help support Hetz’ study of protein misfolding and mislocation in amyotrophic lateral sclerosis (ALS).
The primary mechanism underlying nerve cell (motor neuron) death in ALS remains unknown. One hypothesis suggests that alterations in protein folding functions in a cellular compartment called the endoplasmic reticulum(ER) determine the aggregation and neurotoxicity of ALS-linked mutant SOD1 protein.
Hetz and colleagues have preliminary data that shows specific ER folding mediators called foldases are involved in cellular protection both in models of ALS and in human sporadic ALS spinal cord samples.
The team has demonstrated that induction of ER stress in motor neurons triggers a dramatic misfolding of normal SOD1 protein, resembling recent observations described in sporadic ALS-affected tissue. The investigators uncovered components of the stress pathway that mediate the abnormal misfolding of SOD1 and identified three foldases that can cause normal SOD1 to misfold.
In his new work, Hetz aims to define the impact of specific foldases on motor neuron dysfunction, and assess the possible therapeutic benefits of manipulating them in ALS.
“Since protein folding stress is a common event observed in familial and sporadic cases, our research may open novel possibilities for disease intervention in the near future,” Hetz said.
Grantee: ALS - Claudio Hetz, Ph.D.
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Grant - Spring 2014 - CMT - Ludo Van Den Bosch, Ph.D.
Ludo Van Den Bosch is investigating the possible use of a compound known as an HDAC6 inhibitor in treating type 2F CMT and possibly other disorders of the nervous system.
Charcot-Marie-Tooth Disease (CMT)
Ludo Van Den Bosch, a professor in the Department of Neurosciences at KU Leuven in Leuven, Belgium, was awarded an MDA research grant totaling $235,020 over three years to study the type 2F form of Charcot-Marie-Tooth disease (CMT) and investigate a possible treatment for it. Van Den Bosch and colleagues will conduct experiments in mice with a disorder mimicking human CMT2F, which have been shown to benefit from treatment with a compound known as a histone deacetylase 6 (HDAC6) inhibitor. They hope to find that HDAC6 inhibition has the potential to treat CMT2F and possibly other disorders of the nervous system, including perhaps other forms of CMT.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT - Ludo Van Den Bosch, Ph.D.
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Grant - Spring 2014 - CMT - Gavriel David, M.D., Ph.D.
Gavriel David, an associate professor of physiology and biophysics at the University of Miami’s Miller School of Medicine in Florida, has been awarded an MDA research grant totaling $253,800 over three years to study calcium overload in nerve cells in Charcot-Marie-Tooth disease (CMT). David and colleagues have previously studied mice with CMT-causing genetic defects that disrupt the myelin sheath that coats nerve fibers, finding that disrupted myelin sheaths are associated with abnormally large increases in calcium in nerve cells. Now, they will investigate the apparent relationship between disrupted myelin and calcium overload, with an eye to treating CMT.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT - Gavriel David, M.D., Ph.D.
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Grant - Winter 2012 - ALS — Brian Kraemer, Ph.D.
MDA has awarded a research grant totaling $316,557 over a period of three years to Brian Kraemer, a research biologist in the Geriatrics Research Education and Clinical Center at the Veterans Affairs Puget Sound Health Care System in Seattle.
The funds will help support Kraemer's study of the connection between mutated TDP43 protein and motor neuron (nerve cell) degeneration in amyotrophic lateral sclerosis (ALS).
Abnormal TDP43 protein has been observed in the affected brain and spinal cord nerve cells in people with ALS, and mutations in the gene for TDP43 have been shown to cause inherited ALS in some families.
The way in which abnormalities in the TDP43 protein cause nerve cells to die in ALS remains unclear, Kraemer said, noting, however, thatphosphorylation, or the “addition of [chemicals called] phosphates, to TDP43 at abnormal positions is the most constant hallmark of ALS-related nerve cell destruction seen in post-mortem examination of the nervous systems of affected patients.”
Kraemer and colleagues plan to identify the proteins responsible for TDP43 phosphorylation. Then, in a mouse model of ALS, the investigators will test whether inhibition of the abnormal addition of phosphates to TDP43 could be a valid neuroprotective strategy for ALS.
Grantee: ALS — Brian Kraemer, Ph.D.
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Grant - Spring 2014 - CMT - Elisabetta Babetto, Ph.D.
Elisabetta Babetto, a postdoctoral research scholar at Washington University in St Louis, was awarded an MDA research development grant totaling $152,280 over three years to study the possible role of a protein called PHR1 in degeneration of nerve fibers in Charcot-Marie-Tooth disease (CMT). In experiments in mice with a CMT-like disorder, Babetto will see whether manipulating the biochemical pathway associated with the PHR1 protein can improve the health of nerve fibers. “These experiments will improve our understanding of axonopathy [nerve fiber abnormalities] and have the potential for novel treatments in CMT patients,” she says.
Funding for this MDA grant began May 1, 2014
Grantee: CMT - Elisabetta Babetto, Ph.D.
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Grant – Winter 2013 – FA - Marek Napierala, Ph.D.
Marek Napierala, assistant professor of molecular carcinogenesis at the MD Anderson Cancer Center of the University of Texas, Smithville, was awarded an MDA research grant totaling $320,451 over a period of three years to develop new models of Friedreich’s ataxia (FA) and explore new therapeutic approaches for the disease.
FA is caused by an increase in the number of short DNA sequences, termed GAA repeats, within a gene that encoded for the frataxin protein. This reduces the amount of frataxin that can be made in cells, a problem especially important in neurons (nerve cells) and heart muscle cells. These cells die during the course of the disease, leading to the symptoms of FA.
Napierala studies DNA-editing enzymes called zinc finger nucleases (ZFNs) that can target specific DNA sequences and, operating like a pair of molecular scissors, cut out disease-causing mutations. He will develop cell lines from patients with FA, and then use this technology to repair the gene within the cells.
“Editing the genome of FA cells via excision of the pathogenic expanded GAA repeats,” Napierala says, “will generate a perfect model system: ‘Patient neurons’ can be compared to ‘corrected patient neurons’ derived from the same individual, thus eliminating troublesome variability associated with analyses of patient/control pairs from separate, genetically different individuals.”
The technique will allow him to explore how cells respond when the defect is corrected, and to look for new targets for therapeutic intervention in the disease. In addition, it will establish methods that may be used for similar purposes in other repeat diseases, including myotonic muscular dystrophy (MMD or DM).
Funding for this MDA grant began Feb. 1, 2013.
Grantee: FA - Marek Napierala, Ph.D.
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Grant - Summer 2013 - DMD — Douglas Millay, Ph.D.
Douglas Millay, a postdoctoral researcher at the University of Texas Southwestern Medical Center in Dallas, was awarded an MDA development grant totaling $180,000 over a period of three years to study the process ofmyoblast fusion.
Mature muscle fibers form from the fusion of individual cells, calledmyoblasts. Myoblast fusion occurs both during development and during repair of muscle in later life. Because it is such a central process in muscle repair, understanding myoblast fusion is important for understanding how muscles in muscular dystrophies first repair themselves, and then ultimately exhaust their self-repair ability.
Millay is studying a gene called myomaker, which is an essential component for myoblast fusion, helping to control the timing and location of the fusion process. “Using mouse models and primary muscle cells, we will study the function of this protein in muscular dystrophy disease progression,” he says. “These studies will reveal general mechanisms of mammalian myoblast fusion, expanding our knowledge of this process and identifying avenues for future therapeutic intervention.”
That intervention might take the form of cell-based therapies, in which myoblasts are transplanted into diseased muscle. While this approach has been tried unsuccessfully in the past, a better understanding of the molecules directly mediating myoblast fusion may increase the chances of success, Millay says.
Funding for this MDA grant began August 1, 2013.
Grantee: DMD — Douglas Millay, Ph.D.
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Grant - Spring 2014 - CMT - Anthony Antonellis, Ph.D.
Anthony Antonellis, an assistant professor of human genetics and neurology at the University of Michigan in Ann Arbor, was awarded an MDA research grant totaling $253,800 over three years, to study how mutations in genes that code for specific enzymes cause Charcot-Marie-Tooth disease (CMT). Antonellis and colleagues will conduct experiments in cells to see how genes for enzymes called tRNA synthetases lead to CMT-causing abnormalities and whether restoring the function of these enzymes could be beneficial in treating CMT.
Funding for this MDA grant began May 1, 2014.
Grantee: CMT - Anthony Antonellis, Ph.D.
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Grant – Winter 2013 – DMD, General MD - Radbod Darabi, M.D., Ph.D.
Radbod Darabi, assistant professor of medicine at the University of Minnesota in Minneapolis, was awarded an MDA research grant totaling $380,049 over a period of three years to develop methods to use cells derived from skin to regenerate muscle tissue in a model of Duchenne muscular dystrophy (DMD).
A promising strategy to repair damaged muscles in DMD is to transplant healthy cells into the muscle. One source for such cells is from stem cells, which can be grown in a laboratory dish and treated to become muscle cells. In addition, stem cells can generate muscle satellite stem cells, which are normally found in healthy muscle and are necessary for long-term muscle regeneration.
Recent developments in stem cell biology have allowed researchers to generate induced pluripotent stem cells (iPS cells) from skin cells. Darabi has demonstrated that human skin-derived iPS cells are able to differentiate into muscle and can be successfully transplanted into mice that model DMD. The mice are able to accept the new cells, and the cells produce the dystrophin protein. Lack of dystrophin causes the symptoms of DMD.
“This strategy opens a new window of opportunity to use patient-specific pluripotent stem cells for disease modeling as well as cell therapy for muscular dystrophies,” Darabi says.
His work will include optimizing cell delivery and survival strategies, as well as exploring whether treating cells before transplantation with a regulatory gene can improve the long-term success of the graft. The gene, called PAX7, is a master regulator of muscle satellite stem cells.
Darabi says his research is aimed at making cell transplantation a viable treatment in DMD. “Answering these questions will be crucial for the evaluation of the therapeutic potential of human iPS cells, and consequently moving this strategy one step closer to future clinical trials in muscular dystrophy patients.”
Funding for this MDA grant began Feb. 1, 2013.
Grantee: DMD, General MD - Radbod Darabi, M.D., Ph.D.
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Grant – Winter 2013 – DMD, BMD - Joseph Beavo, Ph.D.
Joseph Beavo, professor of pharmacology at the University of Washington in Seattle was awarded an MDA research grant totaling $412,500 over a period of three years to study how the drug sildenafil acts to improve the function of heart muscle in animal models of Duchenne muscular dystrophy (DMD).
Sildenafil is best known as the brand-name drug Viagra, used to treat erectile dysfunction. But it also can help protect muscles from damage in models of DMD and other diseases. One of the most important muscles researchers hope to protect is the heart muscle.
“At present, there are no effective treatments for most of the cardiac pathology in DMD patients,” Beavo says. Recent work from his group and others strongly suggests that sildenafil improves much of the dysfunction seen in older mdx mice (an animal model of DMD), “potentially opening a new therapeutic treatment for the cardiac pathology seen in muscular dystrophy,” he says.
“In these early studies, it is not clear how this drug works at a molecular level to improve cardiac function,” Beavo says. While much is known about how the drug affects a cell-signaling molecule called PDE5, evidence is accumulating that this is not the route through which sildenafil benefits the heart. Instead, a less-well-known molecule called PDE1C may be the real target of the drug — a hypothesis that Beavo will test in mice.
The identification of the real target (or targets) for sildenafil is particularly important, as clinical trials of the drug in DMD or Becker muscular dystrophy (BMD) are already in progress. Learning how the drug acts on the heart will help researchers understand the results of those trials.
Until there are effective treatments for DMD and BMD, “it is important to effectively treat the symptoms of the disease,” Beavo says. Agents such as sildenafil that have the potential to influence cardiac muscle health may help lengthen and improve the quality of life for people with either DMD or BMD.
Funding for this MDA grant began Feb. 1, 2013.
Grantee: DMD, BMD - Joseph Beavo, Ph.D.
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Grant - Spring 2014 - CMD/LGMD - Maria Chiara Manzini, Ph.D.
Maria Chiara Manzini, an assistant professor of pharmacology, physiology and integrative systems biology at George Washington University in Washington, D.C., was awarded an MDA research grant totaling $253,800 over three years to identify specific genetic mutations underlying congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) in patients who do not have a genetic diagnosis and to study the effects of these mutations in zebrafish, with an eye to treatment development.
Funding for this MDA grant began May 1, 2014.
Grantee: CMD/LGMD - Maria Chiara Manzini, Ph.D.
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Grant - Spring 2014 - CMD/LGMD - Maria Chiara Manzini, Ph.D.
Maria Chiara Manzini, an assistant professor of pharmacology, physiology and integrative systems biology at George Washington University in Washington, D.C., was awarded an MDA research grant totaling $253,800 over three years to identify specific genetic mutations underlying congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) in patients who do not have a genetic diagnosis and to study the effects of these mutations in zebrafish, with an eye to treatment development.
Funding for this MDA grant began May 1, 2014.
Grantee: CMD/LGMD - Maria Chiara Manzini, Ph.D.
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Grant – Winter 2013 – DMD - Matthew Alexander, Ph.D.
Matthew Alexander, a postdoctoral research fellow in genetics and pediatrics at Harvard Medical School in Boston, Mass., was awarded an MDA development grant totaling $180,000 over a period of three years to study the role of microRNAs in Duchenne muscular dystrophy (DMD).
MicroRNAs (miRNAs) are molecules that interact with genes, including the dystrophin gene. (Mutations in the dystrophin gene are the cause of DMD.) Those interactions help control a wide range of processes in cells.
When the dystrophin gene is mutated, the amount of a miRNA called miR-486 is greatly reduced. This causes changes in a system that regulates muscle growth and development.
“Currently, very little is known about the secondary signaling pathways that are altered as a consequence of dystrophin deficiency, and the roles that micro RNAs play in muscle disease,” Alexander says. His work will explore the effects of reducing miR-486 in the context of dystrophin deficiency in the mdx mouse, a research model of DMD. The goal is to gain a better understanding of the problems for muscles caused by loss of miR-486 in order to develop therapies to avoid or compensate for these problems.
“MicroRNA-based therapeutics, unlike traditional single-gene based drug treatments, are capable of manipulating the expression of entire signaling pathways,” says Alexander. In addition, “they can be delivered in a dose-dependent fashion, and can reach the damaged muscle via intravascular or intramuscular injections,” all potential advantages for developing effective treatment.
Funding for this MDA grant began Feb. 1, 2013.
Grantee: DMD - Matthew Alexander, Ph.D.
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Grant - Additional Grants 2013 - MTM — Valerion Therapeutics
The Muscular Dystrophy Association has awarded $1,195,762 over two years to biotechnology company Valerion Therapeutics (formerly 4s3 Bioscience) for development of a treatment for myotubular myopathy (MTM).
The Concord, Mass., company is developing a therapy for MTM that involves delivering myotubularin — the protein that is deficient in MTM — to muscle fibers using an experimental cell-penetrating strategy.
The award was made through MDA Venture Philanthropy (MVP), the drug development arm of MDA's translational research program.
It will allow the company to continue testing its experimental compound3E10FV-MTM1 in mice and to begin producing a pharmaceutical-grade drug that potentially can be tested in people with MTM.
Grantee: MTM — Valerion Therapeutics
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Grant – Winter 2013 – DMD - Madhuri Hegde, Ph.D.
Madhuri Hegde, executive director of the genetics laboratory and associate professor of human genetics at Emory University School of Medicine in Atlanta, Ga., was awarded a one-year MDA research grant totaling $84,924 to advance methods for newborn screening (NBS) for Duchenne muscular dystrophy (DMD).
Recently, a two-step NBS process was developed for detecting DMD in newborns, with a very high detection rate at relatively low cost. In the first step, a drop of blood is analyzed for the presence of the protein creatine kinase. A high level of this protein is associated with muscle damage. In the second step, newborns with a high protein level receive a genetic test for the mutated gene responsible for DMD.
Detection of a DMD-causing mutation provides families with information for future planning, and as new treatments are developed, allows the earliest possible treatment for their child. “Therefore, it is in the best interest of the patients, families and the nation to provide an efficient newborn screening method for DMD to reduce further burden,” says Hegde.
Her project will further refine the two-step screen, using new gene detection techniques to speed analysis. “Our study will help establish a high-throughput, low-cost screening method which can be implemented in NBS programs to efficiently rule out the false positives detected by the creatine kinase level testing,” she says. “The project is aimed to ultimately reduce DMD disease burden.”
Funding for this MDA grant began Feb. 1, 2013.
Grantee: DMD - Madhuri Hegde, Ph.D.
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MDA Resource Center: We’re Here For You
Our trained specialists are here to provide one-on-one support for every part of your journey. Send a message below or call us at 1-833-ASK-MDA1 (1-833-275-6321). If you live outside the U.S., we may be able to connect you to muscular dystrophy groups in your area, but MDA programs are only available in the U.S.
Grant – Winter 2013 – FA - Marek Napierala, Ph.D.
Marek Napierala, assistant professor of molecular carcinogenesis at the MD Anderson Cancer Center of the University of Texas, Smithville, was awarded an MDA research grant totaling $320,451 over a period of three years to develop new models of Friedreich’s ataxia (FA) and explore new therapeutic approaches for the disease.
FA is caused by an increase in the number of short DNA sequences, termed GAA repeats, within a gene that encoded for the frataxin protein. This reduces the amount of frataxin that can be made in cells, a problem especially important in neurons (nerve cells) and heart muscle cells. These cells die during the course of the disease, leading to the symptoms of FA.
Napierala studies DNA-editing enzymes called zinc finger nucleases (ZFNs) that can target specific DNA sequences and, operating like a pair of molecular scissors, cut out disease-causing mutations. He will develop cell lines from patients with FA, and then use this technology to repair the gene within the cells.
“Editing the genome of FA cells via excision of the pathogenic expanded GAA repeats,” Napierala says, “will generate a perfect model system: ‘Patient neurons’ can be compared to ‘corrected patient neurons’ derived from the same individual, thus eliminating troublesome variability associated with analyses of patient/control pairs from separate, genetically different individuals.”
The technique will allow him to explore how cells respond when the defect is corrected, and to look for new targets for therapeutic intervention in the disease. In addition, it will establish methods that may be used for similar purposes in other repeat diseases, including myotonic muscular dystrophy (MMD or DM).
Funding for this MDA grant began Feb. 1, 2013.
Grantee: FA - Marek Napierala, Ph.D.
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