MDA has announced the award of 13 new grants totaling $2.6 million as part of its continued commitment to finding treatments and cures for the diseases in its program. Each of the 13 new grants funds a project that aims to increase our understanding of the causes or underlying mechanisms of neuromuscular disease or potential avenues for therapies to treat these diseases.

Five of the new awards are research grants awarded to established, independent investigators; five are development grants awarded to investigators at the beginning of their careers and on the brink of becoming independent investigators; and three are research infrastructure grants awarded to fund the development of tools, techniques or services to facilitate therapy development.

Each of the new projects could be a step that will lead to new treatments and cures.

Disease understanding speeds therapy development

Knowing what causes a disease and understanding the processes that drive disease progression can help scientists determine possible strategies and targets for treatments. All of the projects funded by the new grants will provide insight and seek answers to important questions such as:

• What causes TDP-43 protein to gather into aggregates (clumps) in ALS (amyotrophic lateral sclerosis), and could blocking the formation and spread of these aggregates provide clinical benefit in people with the disease?
• What triggers muscle dysfunction in central core disease (CCD) and other similar neuromuscular diseases?
• Could CRISPR/Cas9 gene editing technology normalize expression of the LAMA2 gene to help restore stability and organization of skeletal muscle and nerves in merosin-deficient congenital muscular dystrophy (CMD)?
• What underlies the process of fibrosis (scarring) in Duchenne muscular dystrophy (DMD), and could inhibiting the activity of the NOX4 gene protect DMD-affected muscle from fibrotic damage?
• Are synaptic abnormalities responsible for speech dysfunction and fatigue early in the course of Friedreich’s ataxia (FA) and, if so, could targeting treatments to stop or reverse these abnormalities ameliorate symptoms in FA?

Grant highlights

In addition to finding answers to these and other pressing questions, some of the new grants will help identify disease-causing genes and make it easier for people with neuromuscular disease to get a confirmed genetic diagnosis, others represent new partnerships and collaborations, and many have implications across diseases.

Highlights include:

Lukasz Sznajder, Ph.D., a postdoctoral associate at the University of Florida College of Medicine in Gainesville, Fla., was awarded an MDA development grant to apply next-generation sequencing and other technologies to develop novel and disease-specific blood biomarkers for “repeat expansion diseases” (diseases that are caused by the abnormal expansion of particular stretches of DNA). These include ALS and frontotemporal dementia (FTD) caused by a mutation in C9ORF72 and type 2 myotonic dystrophy (DM2).

“Novel therapeutic approaches for the neurological and neuromuscular diseases caused by the expansion of repetitive elements in the human genome are being tested on a daily basis in many research laboratories, and this activity will not stop until effective therapies for these diseases are available,” Sznajder says.

Kristi Wharton, Ph.D., professor of biology at the Brown University Institute for Brain Science in Providence, R.I., was awarded an MDA research grant. In this new academic-industry partnership, Wharton is working to identify novel drug targets for ALS that might quickly be developed using the resources available at Pfizer.

The proposed Brown/Pfizer collaboration takes advantage of each team’s respective strengths and expertise, Wharton says. Brown researchers contribute their experience in generating and evaluating human disease models and screening, while Pfizer researchers contribute their deep knowledge of treatment strategies, their proprietary chemogenomics library of a diverse set of compounds with known physicochemical properties, their screening expertise and an array of molecular reagents.

MDA and the Target ALS Foundation announced a partnership in September 2016. Now, MDA has partnered again with Target ALS to provide $100,000 in support to advance the ALS Biomarker Collaboration.

Data will be shared in an open-access manner to benefit industry as well as the wider ALS community.

Stephan Zuchner, M.D., Ph.D., chairman of the Dr. John T. Macdonald Foundation of Human Genetics at the University of Miami School of Medicine in Florida, was awarded an MDA research infrastructure grant to expand and make more widely available resources to streamline gene identification for diagnostics and therapy development efforts for Charcot-Marie-Tooth disease (CMT).

In collaboration with the Inherited Neuropathy Consortium, Zuchner is working to develop a genomic data infrastructure platform. This open CMT genetics data resource will allow for aggregation, archiving, analysis, comparison and sharing of genetic data among many laboratories and institutions. The resource could speed CMT research from gene identification to therapy discovery and development.

Marta Margeta, M.D., Ph.D., associate professor of pathology at University of California San Francisco School of Medicine, was awarded an MDA research grant to improve understanding of the cellular and molecular pathways by which dysregulation of a process called autophagy impairs skeletal muscle function and leads to muscle injury in sporadic inclusion-body myositis (IBM) and other neuromuscular diseases.

“Both autophagy impairment and excessive autophagy activation play a role in many human diseases including cancer and Parkinson’s disease,” Margeta says. “In the neuromuscular disease field, autophagy impairment plays a role in centronuclear myopathies and lysosomal storage myopathies such as Pompe disease (AMD). Our work has a potential to affect all these disparate research areas.”

Daniel MacArthur, Ph.D., co-director of medical and population genetics at the Broad Institute of Harvard and MIT in Cambridge, Mass., was awarded an MDA research infrastructure grant to create a neuromuscular disease-specific platform for the Rare Genome Project, which will provide more individuals living with neuromuscular diseases access to a definitive diagnosis through advanced genome sequencing techniques.

The low prevalence of similar rare muscle disease patients means that recruiting for a study with in-person visits is often infeasible, MacArthur says. Working with MDA, the Broad Institute has developed the Rare Genomes Project to give patients the opportunity to participate in a research study no matter where they live.

Robert Bryson-Richardson, Ph.D., associate professor at the School of Biological Sciences, Monash University, in Victoria, Australia, was awarded an MDA research grant to investigate potential approaches to treating myofibrillar myopathy (MFM) caused by a mutation in the Filamin C gene.

“We are testing multiple drugs in our animal model,” Bryson-Richardson says. “Some of these, if effective, could be suitable for clinical use. Those that are not suitable for clinical use will help us to identify pathways that could be targeted in future therapies.”

Feeding the pipelines for today and tomorrow

In this era of unprecedented progress in neuromuscular disease research and care, MDA is working hard to keep the therapy and neuromuscular disease researcher pipelines full.

With these latest grants and other active MDA grants — funding about 160 research projects around the world — we’re keeping hope alive today and contributing to the development of drugs that will transform lives tomorrow.

Explore the 2018 Winter Grants