Innovations in Science
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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Grants - Spring 2014 - ALS - Stanley Appel, M.D.
Stanley Appel, a professor of neurology at Methodist Neurological Institute in Houston, was awarded an MDA research grant totaling $253,800 over three years to study immune mechanisms in amyotrophic lateral sclerosis (ALS). Experiments previously conducted by Appel and colleagues in mice with an ALS-like disorder have shown that the immune system acts to protect nerve cells during the early stages of the disease but that it damages nerve cells in the disorder’s later stages. The mouse studies suggest that manipulating aspects of the immune system could improve ALS outcomes. With the new funding, Appel will investigate whether the same immunologic changes seen in the mice occur in ALS patients and whether they follow the same time course. If so, these “immune hallmarks,” Appel says, have the potential to be used as biological indicators of the effectiveness of therapies that alter the immune system.
Funding for this MDA grant began May 1, 2014.
Grantee: ALS - Stanley Appel, M.D.
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Grant - Spring 2014 - CMS/LGMD/PP - Jocelyn Laporte, Ph.D.
Jocelyn Laporte, a team leader at the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France, was awarded an MDA research grant totaling $253,800 over three years to develop drugs to treat certain types of congenital myasthenic syndromes (CMS), limb-girdle muscular dystrophy (LGMD) and periodic paralysis (PP) . Using cells taken from patients with these disorders and animals with conditions mimicking these disorders, Laporte and his colleagues will test the effects of drugs that act on the flow of calium. They will investigate whether drugs that act on cellular calcium should be developed as treatments for various muscle disorders and possibly for muscle aging.
Funding for this MDA grant began May 1, 2014.
Grantee: CMS/LGMD/PP - Jocelyn Laporte, Ph.D.
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Grant - Summer 2012 - CMD — Kevin Campbell, Ph.D.
MDA awarded a research grant totaling $375,000 over three years to Kevin Campbell, professor of neurology and internal medicine at the University of Iowa in Iowa City. The funds will help support Campbell's study of a process called protein O-mannosylation in a mouse model of congenital muscular dystrophy (CMD).
O-mannosylation is an important protein modification that occurs in mammals. Diseases caused by O-mannosylation defects include severe muscular dystrophies characterized by profound muscle weakness as well as central nervous system impairment. Despite extensive efforts, the genetic causes of most occurrences of these diseases remain unknown.
The only known O-mannosylated protein is alpha-dystroglycan, which works in skeletal muscle to link connective tissue (the extracellular matrix) with the cellular framework or "scaffolding" known as the cytoskeleton.
Campbell aims to identify proteins that play a role in initiating O-mannosylation and then investigate their function in cell culture models. He also is working to generate a new O-mannosylation-deficient mouse model in which to study any newly identified proteins.
There is a critical need for better understanding of the mechanism responsible for this modification to develop new treatment options for O-mannosylation deficient disease, Campbell says. "Besides direct patient health benefits, identification of new players involved in protein O-mannosylation will open new avenues to understand O-mannosylation deficient muscular dystrophies."
Funding for this MDA grant began Aug. 1, 2012.
Grantee: CMD — Kevin Campbell, Ph.D.
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Grant - Summer 2013 - DMD — Charles Gersbach, Ph.D.
Charles Gersbach, assistant professor at Duke University in Durham, N.C., was awarded an MDA research grant totaling $300,000 over a period of three years to develop a new approach for gene therapy in Duchenne muscular dystrophy (DMD).
The most common gene therapy approaches in DMD involve supplying new dystrophin genes (the dystrophin gene is mutated in the disease), allowing the new genes to integrate into existing chromosomes or to remain outside the chromosomes. The first approach can potentially disrupt other genes, while the second only provides temporary therapy that requires frequent re-administration, raising risks.
“An exciting alternative to these approaches is a new technology, called genome editing, that can target the addition of therapeutic genes to specific sites in the genome or directly repair the disease-causing mutations [in existing genes],” says Gersbach. The technique is already being tested in early-stage clinical trials in HIV and cancer.
Genome editing holds the potential for fixing mutated genes permanently. The approach may apply to all genes and all kinds of mutations, including large deletions.
In this project, the overall objective is to engineer and test enzymes called nucleases to see if they can either deliver the dystrophin gene or repair existing mutant dystrophin gene sequences. The enzymes will be tested in cultured cells from DMD patients and in a mouse model of the disease.
“New technologies for gene delivery and gene modification are overcoming the challenges of translating gene therapy into correction of genetic diseases,” Gersbach says. “These technologies are expected to lead to dramatic advances in gene therapy in the next few years.”
Funding for this MDA grant began August 1, 2013.
Grantee: DMD — Charles Gersbach, Ph.D.
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Grant – Winter 2013 – DMD - Kay Davies, M.A., Ph.D.
Dame Kay Davies, Dr. Lee’s Professor of Anatomy in the department of physiology, anatomy and genetics at the University of Oxford in the United Kingdom, was awarded an MDA research grant totaling $207,566 over a period of two years to conduct a drug screen for molecules that can increase levels of a protein called utrophin, which can be developed for clinical trials in Duchenne muscular dystrophy (DMD).
DMD is caused by a mutation that prevents formation of normal dystrophin protein. “Utrophin is very similar to the missing dystrophin protein,” Davies says, and it is unaffected in DMD. Increasing the amount of utrophin has been shown to be beneficial in a mouse model of DMD, indicating the potential for utrophin-increasing drugs in humans. Drugs may offer benefits that other treatment strategies don’t, she says, since they reach every muscle in the body (which has been a challenge for some other strategies), including the heart and the diaphragm.
Davies' drug development efforts (supported by a previous MDA research grant) already have led to an MDA-supported phase 1 safety trial of a compound called SMT C1100, and further trials are planned. At the same time, Davies wants to develop drugs that do the same job better. “We aim to develop ‘best in class’ drugs to follow on from this,” she says. “We have developed a new, more sensitive screening assay and have already found new hits [drug candidates] that work better than the original drug in tissue culture.” Those now will be tested in mouse models, and tinkered with to optimize their performance.
“We are at an exciting point in this research, and we are optimistic that we will be able to find a drug which will increase levels of utrophin to provide substantial clinical benefit,” Davies says.
Funding for this MDA grant began Feb. 1, 2013.
Grantee: DMD - Kay Davies, M.A., Ph.D.
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Grant - Additional Grants 2012 - Muscular Dystrophies — Center for Genetic Medicine Research (CGMR) — Kanneboyina Nagaraju
The Muscular Dystrophy Association has given a $300,000 grant to the Center for Genetic Medicine Research (CGMR) at Children’s National Medical Center in Washington, D.C., to continue standardized and reliable preclinical studies of neuromuscular diseases.
The MDA Translational Research Grant was awarded to CGMR's Kanneboyina Nagaraju, who directs the Murine Functional Testing Core Facility. It's the largest preclinical drug testing facility for neuromuscular disease models.
The facility helps advance drug development by testing drugs and other experimental treatments in mouse models of neuromuscular disease, allowing researchers to obtain information about how a treatment is likely to influence a disease course.
The U.S. Food and Drug Administration (FDA) generally require this type of preclinical study before it allows new substances to be tested in humans.
Several strains of mice with various neuromuscular diseases are maintained at the facility, including some with rare forms of muscular dystrophy that are not widely available.
Grantee: Muscular Dystrophies — Center for Genetic Medicine Research (CGMR) — Kanneboyina Nagaraju
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Grant - Additional Grants 2013 - DMD/BMD — Jeffrey Chamberlain, Ph.D.
Jeffrey Chamberlain, a molecular biologist at the University of Washington, Seattle, was awarded an MDA grant of $328,628 over one year (through Jan. 31, 2014) to develop gene therapy delivery vehicles ("vectors") for gene transfer in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Chamberlain will develop gene transfer vectors derived from adeno-associated viruses (AAVs). They'll be designed to carry miniaturized versions of the gene for the dystrophin protein, which is missing in DMD-affected muscles and deficient in muscles affected by BMD. The studies are directly related to moving gene therapy for DMD/BMD into clinical trials.
Grantee: DMD/BMD — Jeffrey Chamberlain, Ph.D.
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Grant - Spring 2014 - ALS - Muralidhar Hegde, Ph.D.
Muralidhar Hegde, a professor at the Houston (Texas) Methodist Research Institute, was awarded an MDA research grant totaling $253,800 over three years to study whether deficient repair of DNA strand breaks by a protein called TDP43 is involved in amyotrophic lateral sclerosis (ALS) causation. Hegde will conduct experiments in mouse and human cells and says the result could lead to a “major paradigm shift in our understanding of ALS pathology” and “open up new avenues for therapeutic interventions.”
Funding for this MDA grant began May 1, 2014.
Grantee: ALS - Muralidhar Hegde, Ph.D.
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Grant - Additional Grants 2013 - DMD/BMD — ARMGO Pharma
MDA has awarded $1 million to biopharmaceutical company ARMGO Pharma for development of a new strategy for treating Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD).
The award supports laboratory work that will enable the company to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration. (An IND application is a step a company must take before it can test a new drug in humans.) Receiving an IND approval will allow ARMGO Pharma to prepare for clinical trials with ARM210 in healthy volunteers and for subsequent clinical studies in people with DMD.
The experimental class of compounds — which ARMGO calls Rycal drugs — is designed to normalize the way skeletal muscle fibers and heart muscle cells handle calcium.
The lead compound, ARM210, is aimed at treating DMD or BMD, which are caused by mutations in the dystrophin gene. However, the strategy is not dependent on the specific disease-causing genetic mutation and potentially could have application to other muscle disorders.
Grantee: DMD/BMD — ARMGO Pharma
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