On Oct. 28, 2021 the Muscular Dystrophy Association (MDA) announced the awarding of 18 new grants totaling over $1.6 million toward neuromuscular disease (NMD) research. These new grants represent a continued commitment by MDA to fund groundbreaking research that will one day lead to treatments and cures for the diseases in its program. The newly funded projects aim to advance research and therapy development in multiple areas including amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), Charcot Marie Tooth disease (CMT) and myotonic dystrophy.
Answering crucial questions to speed therapy development
This grant cycle builds upon decades of MDA-backed research that has led to a better understanding of the different NMDs, as well as a number of FDA-approved treatments. The awarded grants will fund studies to advance our understanding of the causes of NMDs and investigate new therapeutic approaches to treat NMDs. MDA is also committed to maintaining a robust pipeline of promising early-stage investigators who will make the important discoveries of the future.
The 2021 MDA grants have been awarded in two categories: Development Grants and Idea Awards. Seven Development Grants will be given to investigators at the beginning of their careers who are on the brink of becoming independent investigators. Additionally, 11 Idea Awards will fund bold, innovative research ideas that are expected to greatly impact the field of neuromuscular disease.
This round of grant funding reinforces MDA’s unwavering commitment to the progress of NMD research and builds on the more than $1 billion MDA has already invested in research to uncover new treatments and cures for NMDs since its inception.
“These grants do two very important things – help grow the next generation of neuromuscular disease investigators and provide seed funding for those creative, hard-to-fund projects that just need a little boost at this early stage,” said Sharon Hesterlee, PhD, Chief Research Officer, MDA.
Highlights from the grant awards for this grant cycle include:
Alba Timón-Gómez, PhD
Role of mitochondrial hypoxia inducible factors in respiratory chain biogenesis
Miller School of Medicine of the University of Miami
The muscles and brain have high energy demands, which makes them the most affected organs in mitochondrial disorders. Findings from this work could help gain insights into the pathogenesis of mitochondrial encephalomyopathies.
Jae-Sung You, PhD
Targeting Leucyl-tRNA synthetase and autophagy in Duchenne muscular dystrophy
The Board of Trustees of the University of Illinois at Urbana-Champaign
Studies have shown that an autophagy suppressor, mammalian target of rapamycin complex 1 (mTOR1), was observed in mouse and human DMD skeletal muscles. It has also been shown that inhibition of mTOR1 by rapamycin or low protein diet that autophagy was rescued and improved dystrophic phenotypes in DMD mice. Dr. You’s work will help fill in the current knowledge gap in DMD pathology and discover new therapeutic targets for the treatment of the disease.
“MDA’s development grant allowed me to investigate the pathogenic mechanisms of Duchenne muscular dystrophy and its potential therapeutic targets and helped me establish my early career in neuromuscular disease research,” said You.
Valérie Allamand, PhD
Suppression of COL6 premature termination codons by anticodon-edited tRNAs
COL6 mutations that introduce premature stop codons show the most severe clinical presentations. Individuals who are affected by these mutations, about 10% of patients with COL6-RD, typically do not have COL6 synthesized in the extracellular matrix. Dr. Allamand will correct the production of COL6 by using anticodon engineered tRNAs. The findings will provide data for in vivo approaches on treated cells and pre-clinical studies in COL6-RD mouse models with nonsense mutation. Additionally, the technique used in this project can be applied to other neuromuscular diseases caused by nonsense mutations.
“The funded project relies on a collaboration with Dr. Christopher Ahern (University of Iowa, Iowa City, IA) who published in 2019 a very elegant approach to correct premature termination codons (PTC). My group in the Research Center in Myology (Paris, France) focuses on congenital muscular dystrophies (CMD), notably COL6-related diseases (COL6-RD). The grant will allow us to assess the efficacy of Dr. Ahern’s approach in cells (fibroblasts) derived from patients’ skin biopsies. The next step will be to move to a mouse model developed in my group. This research is important to me because I believe that the results obtained can have a significant impact on patients’ lives,” said Dr. Allamand. “I am very grateful to MDA for this Idea Grant Program that will enable us to obtain in vitro proof-of-concept results and hopefully move quickly to pre-clinical studies. Developing therapeutic strategies for patients is our motivation and the grant allows us to move forward with this promising strategy that we plan on developing also for other types of CMDs.”
Nick Menhart, PhD
Computational Design of Modified Dystrophins
Illinois Institute of Technology
Exon skipping can only occur at exon skipping areas, which can lead to protein structure instability. Dr. Menhart’s lab discovered that edit-mediated structural disruption did not occur near the edit site, but rather located outside of the edit side and exhibited at domain junctions. With their computational framework, they can search for new ways to edit the dystrophin message that may produce better, more functional modified dystrophin proteins than the options available with skipping specific exons.
2021 MDA Research Grants
- Frederick Arnold; The RNA exosome complex in ALS disease pathogenesis; The Regents of the University of California (Irvine)
- Daniel Calame; Uncovering the Genomic Architecture of Undiagnosed Neuromuscular Disease; Baylor College of Medicine
- Junio Dort; Beneficial impact of resolving-D2 pm Duchenne muscular dystrophy; Centre Hospitalier Universitaire Sainte-Justine
- Narendra Jha; Identification of modifier gene(s) of spinal muscular atrophy in model mice; Columbia University Medical Center
- Xin Jiang; Blocking RAN translation to rescue C90RF72-related ALS/FTD phenotypes; Massachusetts General Hospital
- Alba Timón-Gómez; Role of mitochondrial hypoxia inducible factors in respiratory chain biogenesis; Miller School of Medicine of the University of Miami
- Jae-Sung You; Targeting Leucyl-tRNA synthetase and autophagy in Duchenne muscular dystrophy; The Board of Trustees of the University of Illinois at Urbana-Champaign
- Matthew Avenarius; Identifying novel SMA-causing variants by NGS sequencing of the SMN1 locus; The Ohio State University
- Stefano Biressi; Jag1 gene therapy in muscular dystrophies; University of Trento
- Alexandre Blais; Glucocorticoid receptor and muscle stem cell quiescence; University of Ottowa
- Joshua Burns; Establishing a network of highly trained and reliable CMT clinical evaluators; The University of Sydney
- Andrew Geronimo; Assessment of nocturnal hypoventilation in amyotrophic lateral sclerosis; The Pennsylvania State University College of Medicine
- Nick Menhart; Computational design of modified dystrophins; Illinois Institute of Technology
- Joseph Metzger; Novel high throughput method to assess micro-dystrophin turnover in muscle; Regents of the University of Minnesota-Twin Cities
- Emma Rybalka; Repurposing dimethyl fumarate for the treatment of Duchenne muscular dystrophy; Victoria University
- Tanja Taivassalo; Measuring cardiopulmonary responses to the 6MWT and peak effort exercise in DMD; University of Florida
- Massimo Delledonne; Innovative technologies to unravel the complexity of myotonic dystrophy repeats; University of Verona
- Valérie Allamand; Suppression of COL6 premature termination codons by anticodon-edited tRNAs; Sorbonne Université-Inserm
About the Muscular Dystrophy Association
For 70 years, the Muscular Dystrophy Association (MDA) has been committed to transforming the lives of people living with muscular dystrophy, ALS, and related neuromuscular diseases. We do this through innovations in science and innovations in care. As the largest source of funding for neuromuscular disease research outside of the federal government, MDA has committed more than $1 billion since our inception to accelerate the discovery of therapies and cures. Research we have supported is directly linked to life-changing therapies across multiple neuromuscular diseases. MDA’s MOVR is the first and only data hub that aggregates clinical, genetic, and patient-reported data for multiple neuromuscular diseases to improve health outcomes and accelerate drug development. MDA supports the largest network of multidisciplinary clinics providing best-in-class care at more than 150 of the nation’s top medical institutions. Our Resource Center serves the community with one-on-one specialized support, and we offer educational conferences, events, and materials for families and healthcare providers. MDA Advocacy supports equal access for our community, and each year thousands of children and young adults learn vital life skills and gain independence at summer camp and through recreational programs, at no cost to families. During the COVID-19 pandemic, MDA continues to produce virtual events and programming to support our community when in-person events and activities are not possible. MDA’s COVID-19 guidelines and virtual events are posted at mda.org/COVID19. For more information, visit mda.org.