Research for a Cure
The Myotonic Dystrophy Foundation (MDF) supports scientific investigations to enhance the quality of life of people living with myotonic dystrophy and advance research focused on finding treatments and a cure for this disease. As a part of this effort, the MDF offers a number of funding opportunities for DM researchers and supports research efforts.
Grantwriting Training for Researchers
The Myotonic Dystrophy Foundation hosted a grant writing training at the 2014 MDF Annual Conference, presented by Dr. John Porter, PhD, former Program Director at NINDS/NIH. Click here to view the PowerPoint presentation from that training and access best-in-class grantwriting tips.
2024 Myotonic Dystrophy Foundation Research Grant RFA
More information coming Spring 2023.
For more information on MDF grantmaking policies, click here to read the MDF Request for Proposals Award Policy manual.
Email the Myotonic Dystrophy Foundation's Research Coordinator, Nadine Skinner, PhD, MPA.
2023 MDF Grant Recipients
The Myotonic Dystrophy Foundation US made the following grants in 2023:
2023 MDF Early Career Researchers
Dylan Farnsworth, PhD
Senior Research Scientist
The RNA Institute, University of Albany, New York, US
Myotonic dystrophy (DM) disrupts gene expression across almost all organ systems. Within these organs, there are many distinct cell types formed by the expression of genes that are specific to a cell’s function. For example, muscle, bone, and intestinal cells all express a different set of genes, which will all be affected differently by the DM repeat expansion. In order to understand how the DM mutations cause symptoms, researchers must first understand which cells express the genes that lead to DM, and second, how the expression of all genes required by these cells is affected in DM. One of the best ways to address this issue is using zebrafish, a vertebrate model organism with recreated genetic mutants that cause DM in humans. This can simultaneously allow researchers to analyze the gene expression patterns of many cell-types across the entire animal. In the project, “Connecting cell-type specific gene-expression patterns in DM-model zebrafish to sleep and circadian disruptions and enhanced therapeutic development”, Dr. Farnsworth and colleagues will link DM-causing genes with cell-types, and cell-types with symptoms. They will use this knowledge to test drugs on zebrafish that can rescue these cell-type specific gene expression patterns and alleviate DM symptoms. Specifically, zebrafish with DM-associated mutations have defects in gastrointestinal (GI) function and regulation of circadian genes that mirror the digestive symptoms and sleep disruption reported by DM patients. Since drug-testing in zebrafish is very rapid and accessible, they will test currently available drugs for their ability to alleviate these DM symptoms.
Matteo Garibaldi, MD, PhD
Sapienza University of Rome, Italy
Muscle weakness in myotonic dystrophy type 1 (DM1) is the consequence of progressive fat replacement of muscles. Muscle MRI studies can reveal if muscles are spared or affected. In many muscle diseases fat replacement is preceded by hyperintense signal in specific MRI sequences (STIR), representing a signature of disease ‘activity’. Consequently, muscle MRI can reveal unaffected muscles, actively affected but still unreplaced muscles, and affected muscles. Some muscles in DM1 are early affected while others remain spared in the course of the disease. This phenomenon leads to a disease-specific pattern of muscle involvement detectable by muscle MRI. Dr. Garibaldi and colleagues recently reported muscle MRI data from a large cohort of DM1 patients showing that DM1 muscle involvement is characterized by progressive fat replacement that is preceded by a period of STIR positivity. In the project, “TranSTIRomics for DM1 - Where the disease begins: a muscle MRI-based transcriptome study in myotonic dystrophy type 1”, Dr. Garibaldi and colleagues aim to understand the biological processes occurring in STIR+ muscles by histopathological and transcriptome (gene expression) analyses. This study will reveal novel insights into pathophysiological mechanisms of muscle weakness in DM1. This will allow a better understanding of what happens when the disease begins and provide novel biomarkers and potential therapeutical targets for the earliest stages of disease. The results will be important for timing the start of treatments, allowing for the identification and treatment of patients in the earliest stages of disease, when the disease switches from a quiescence state to the active-pre-symptomatic phase, anticipating fat replacement and preventing muscle weakness.
Melissa Hale, PhD
Virginia Commonwealth University, Richmond, Virginia, US
Children with congenital myotonic dystrophy (CDM) present with a unique set of symptoms compared to adults with myotonic dystrophy type 1 (DM1). Unlike in adults, where muscle symptoms decline with age, CDM muscle symptoms often improve in early childhood. How this change occurs is unknown. To date, most research on this has been defined in the context of adult-onset DM1. However, with the distinct presentation of CDM, it is Dr. Hale’s expectation that other cellular processes may occur in CDM children. To address this hypothesis, she recently performed large-scale RNA sequencing to discover differences in the muscle of CDM children across childhood development using muscle biopsies from 34 CDM individuals from 2 weeks – 16 years of age. To date, this is largest dataset of its kind focused exclusively on CDM. This analysis revealed that markers of muscle cell dysfunction in CDM universally improve in early childhood, often to the level of unaffected children, post-severe disease onset at birth. This matches the period where muscle function improves in patients. The goal of her project, “Defining contribution of muscle stem cell activation to dynamic congenital myotonic dystrophy transcriptome”, is to investigate the contribution of a unique population of cells in skeletal muscle, called muscle stem cells (MuSCs), to the molecular signatures observed. MuSCs represent a unique population of cells embedded in all muscles of the body that can regenerate and repair muscle. An understanding of their activity in CDM across childhood development will not only provide a better understanding of the disease but may illuminate potential new therapeutic targets for the most severely affected patients.
2020 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2020:
“Reach DM- Study to Promote Trial Readiness by Genetic Analysis and Telemedicine Assessments”
PI: Johanna Hamel, MD
University of Rochester, New York, US
This project supports Dr. Johanna Hamel and Dr. Charles Thornton at the University of Rochester to study DM1-affected individuals to determine feasibility for remote genetic testing and disease assessments. This study focuses on 300 individuals who have a clinical diagnosis of DM1 in the MDF and National Registries. The goal of this study is to assess phenotype and genotype remotely and improve understanding of disease variability in DM1. By reversing the conventional directionality of research, which involves patients travelling to research centers, they evaluate people in their homes by sending them a toolkit and conducting virtual research visits via tele-video conferencing. By overcoming financial, geographic, and socioeconomic barriers, this study expands access to research and genetic testing.
2019 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2019:
“Developing novel CRISPR-Cas9 variants for efficient in vivo contraction of CTG/CAG repeats”
PI: Vincent Dion, PhD
Cardiff University, Wales, UK
Gene editing, a way to correct the mutation that causes DM1, provides novel research avenues. Recently, Dr. Dion’s team showed that CRISPR-Cas9, an unparalleled gene editing technology, can contract precisely the expanded CTG/CAG repeat tract, thereby removing the cause of DM1. They found that gently nicking the repeat tract leads to contractions. Administration of the enzyme is difficult and inefficient because it is too large to be packaged into adenoassociated viruses, the delivery method of choice for gene therapies. In this project, they aim to improve the efficiency of Cas9 delivery by reducing the size of the enzyme and to determine its safety by measuring the frequency of unwanted mutations it might cause. Dion will test new Cas9 variants both in human cells and in pre-clinical mouse models. They aim to develop a safe and efficient tool for an eventual therapy based on gene editing.
2018 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2018:
“Myotonic Dystrophy Clinical Research Network (DMCRN) Site Grants: Multicenter Study of Natural History and Genetic Modifiers in Myotonic Dystrophy Type 1”
PI: Nicholas Johnson, MD
Virginia Commonwealth University, Virginia, US
The DMCRN will undertake an ambitious 8-site study of disease progression and genetic modifiers of DM1. The proposed study will use unrestrictive entry criteria, ensuring that any subject with DM1 is included. To meet the increased recruitment demands, the study involves new sites (University of Utah, Salt Lake City and Houston Methodist Neuroscience Institute, Houston, TX) and concise study visits (2-3 hours) that do not include invasive procedures. It is expected that this will drive strong enrollment and allow participation from segments of the community who previously may have felt disenfranchised. As compared to the current study, it examines a larger number of patients (n = 500) over a longer time period (2 years). The outcome measures are a subset of those used in previous studies, selecting those with best performance characteristics. Sites and partners include:
Tetsuo Ashizawa, MD, Houston Methodist Neuroscience Institute, US
John Day, MD, PhD, Stanford University, US
Nicholas Johnson, MD, University of Utah, US
John Kissel, MD, Ohio State University, US
Jeffrey Statland, MD, University of Kansas Medical Center, US
S.H. Subramony, MD, University of Florida, US
Laurie Gutmann, MD, University of Iowa, US
“Development of a Mouse Drug Testing Facility for Myotonic Dystrophy”
PI: Laurent Bogdanik, PhD
The Jackson Laboratory, Bar Harbor, Maine, US
The reliable evaluation of drug candidates upstream of clinical trials relies in most cases on good mouse models that replicate key features of the disease, but also on reliable experimental assays. A robust infrastructure to produce, maintain, distribute and study mouse colonies, connect with drug developers, and prepare and execute in vivo pharmacology studies in a rigorous laboratory environment are also desirable. The goal of Dr. Bogdanik’s project is to make available to the DM drug development community, in a centralized location, the HSA-LR model and future DM mouse models, along with the knowledge resources and the drug testing services that will support the development of tomorrow’s cures.
“Request for Support for Publication and Open Access Fee for a Peer-Reviewed Myotonic Dystrophy Therapy Review Paper”
PI: Ruben Artero, PhD
University of Valencia, Spain
The depth and quality of DM publications, from basic research to review papers, is an essential component to attracting more research and industry engagement to the field. DM publications in high impact journals and in journals with a broad readership, is one of the most effective ways to highlight the disease and unmet need. It is also an effective method to attract a more diverse research base. Dr. Ruben Artero, a well-respected researcher in the myotonic dystrophy field from the University of Valencia, Spain, received a one-time grant to support the publication and open access fees for a review article entitled “Oligonucleotide-based therapies for Myotonic Dystrophy”. The article will be published in Drug Discovery Today.
“Meeting Grant Support for 9th International Conference on Unstable Microsatellites and Human Disease”
PI: Laura Ranum, PhD
University of Florida Continuing Medical Education, US
9th International Conference on Unstable Microsatellites and Human Disease.
2017 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2017:
“Houston Methodist Coordinator Position Grant”
PI: Tetsuo Ashizawa, MD
Houston Methodist Neurological Institute, US
The Myotonic Dystrophy Foundation will provide Houston Methodist Neurological Institute with funds to support a clinic coordinator position at the Ashizawa Lab.
“Biomarker Qualification Project”
Jane Larkindale, DPhil
Critical Path Institute, US
The Critical Path Institute will provide the Myotonic Dystrophy Foundation (MDF) with support with a regulatory strategy for a Drug Development Tool (DDT) qualification pathway for a biomarker for myotonic dystrophy (DM), preparation and regulatory review of submissions to the FDA, support for all interactions with regulators, including preparations for meetings of Biomarker Qualification Review Team (BQRT) and leadership at FDA meetings, as well as keep the MDF updated on all regulatory developments (guidance, webinars, meetings) related to qualification in general and DM and other related neurological disorders in particular.
2016 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2016:
“PicnicHealth Registry Project”
PI: Noga Leviner
PicnicHealth, San Francisco, California, US
This is a proposal to design and execute on a pilot project to 1) collect medical records and 2) structure medical record data for a cohort of 100–200 myotonic dystrophy patients using PicnicHealth’s patient-centered medical records collection and management platform. This pilot study will determine whether the approach is a feasible one for constructing DM patient natural histories.
“Prevalence of Myotonic Dystrophy”
PI: Nicholas E. Johnson, MD
University of Utah, US
This project is a Population-Based Prevalence Study in Myotonic Dystrophy Type-1 and Type-2. The prevalence of myotonic dystrophy type 1 and type 2 are unknown. This is at least partly due to the wide variation in the age of onset and individuals with the disease who have not been diagnosed; both of which would not be accounted for in a traditional prevalence study. To address this issue MDF US and MDF UK issued a two-phase RFA. The phase I RFA was designed to develop an assay that could be used in a population-based screen. The phase II RFA provides funds sufficient to implement a screen in a group representative of the general population, for example, via newborn bloodspots or via banked blood from other ongoing studies as appropriate. In phase I, Dr. Johnson was awarded a grant to develop and validate a cost-effective screening methodology capable of estimating the prevalence of DM1 and DM2 mutations and pre-mutations in the general US population. In phase II, Dr. Johnson’s application received the grant award to use a population sample of de-identified newborn blood spots to determine carriers of DM mutations and pre-mutations. This will provide the first-ever large-scale population-based prevalence study of myotonic dystrophy types 1 and 2.
“Workshop Support - Myotonic Dystrophy: Developing a European Consortium for Care and Therapy”
PI: Alexandra Breukel, PhD
European Neuromuscular Centre, Netherlands
This Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK-supported workshop was focused on establishing a mechanism for international collaboration between expert centers in Europe in order to ensure better coordination for DM clinical trials. Participating centers would share existing, partly unpublished natural history data, refine suitable outcome measures, provide for identification of patient populations and qualify trial sites. Moreover, the establishment of networking of the existing knowledge, infrastructure and personnel would facilitate appropriate inclusion and communication of patients and patient organizations, the interaction with commercial as well as academic trial sponsors and the involvement of regulators and payers along the translational pathway. Foundation interests in this effort include establishing strong partnerships between the new European consortium and the existing Myotonic Dystrophy Clinical Research Network (DMCRN) in the US.
“Building a Better Mouse”
PI: Cathleen Lutz, PhD
The Jackson Laboratory, US
This project will support the development of a new BAC transgenic mouse model of myotonic dystrophy type 1 (DM1) at the Jackson Laboratory (JAX). This will be accomplished by creating a BAC transgenic with a large CTG repeat and a wildtype control. The funding provided will be used to create the model with some baseline clinical observations of weight, survival and overt phenotypes. Using a BAC approach to express the expanded repeat in all tissues will increase the probability of emulating the multi-systemic nature of DM by showing defects in the CNS, heart and other organ systems, as well as muscle. In addition to the need for new models to better understand disease mechanisms, industry views a better DM1 mouse model as essential to its therapeutic development efforts.
“Extracellular RNA as Biomarkers of Myotonic Dystrophy”
PI: Thurman Wheeler, MD
Massachusetts General Hospital, US
A new drug for treatment of DM1 is being tested in clinical trials. Monitoring drug effects currently requires that patients undergo multiple muscle biopsies, a procedure that is invasive, painful and, in pediatric patients, requires general anesthesia. The goal of this project is to develop biomarkers in human urine or blood that:
Will reduce or eliminate the need for muscle biopsies to determine whether treatments are working
Can be measured multiple times as needed during the trial
Enable inclusion of children with DM1 in upcoming trials
The approach will be applicable to many different treatment strategies for both DM1 and DM2.
“DM Cell Line Library”
PI: Michael Sheldon, PhD
RUCDR Infinite Biologics, Rutgers University, US
This grant award is intended to support the development of eight new DM iPSC lines at RUCDR Infinite Biologics for distribution to qualified investigators at academic institutions and biotech/pharmaceutical companies. Numerous companies seeking to develop therapies for DM have reported that they are having difficulty obtaining well-documented cell lines for DM1 and DM2. High-throughput screening programs for small molecule development in other neuromuscular diseases have found results that differ based upon the cell type used in the screen. By making human iPSC cells derived from fibroblasts of patients with expanded repeats (>400) available, researchers and drug developers will be able to derive cell types (e.g. neurons, myocytes, cardiomyocytes) appropriate to their needs. There will be no licensing fees or reach-through on intellectual property, ensuring that commercial development efforts are unhindered.
“Myotonic Dystrophy Clinical Research Network (DMCRN) Site Grants: Multicenter Study of Natural History and Genetic Modifiers in Myotonic Dystrophy Type 1”
During the last project period, the DMCRN completed its first project, a study of natural history and RNA biomarkers in 100 patients with DM1. The DMCRN subsequently expanded the enrollment and expects to have one year follow up data on 100 subjects by the first quarter of 2017. The results of the DMCRN collaboration abundantly confirmed that RNA splicing biomarkers are tightly linked to the disease process and reliable for monitoring disease activity. The methods and data will be taken forward to the FDA for formal qualification of splicing biomarkers as drug development tools for DM1. The DMCRN is now pursuing parallel work for DM2.
The DMCRN will undertake an ambitious 8-site study of disease progression and genetic modifiers of DM1. The proposed study will use unrestrictive entry criteria, ensuring that any subject with DM1 is included. To meet the increased recruitment demands, the study involves new sites (University of Utah, Salt Lake City and Houston Methodist Neuroscience Institute, Houston, TX) and concise study visits (2-3 hours) that do not include invasive procedures. It is expected that this will drive strong enrollment and allow participation from segments of the community who previously may have felt disenfranchised. As compared to the current study, it examines a larger number of patients (n = 500) over a longer time period (2 years). The outcome measures are a subset of those used in previous studies, selecting those with best performance characteristics.
Six DMCRN site awards have been issued (two DMCRN sites - the National Institutes of Health: Ami Mankodi, M.D., and the University of Rochester, Drs. Richard Moxley III, M.D, and Charles Thornton, M.D., - have separate funding sources):
Tetsuo Ashizawa, M.D., Houston Methodist Neuroscience Institute, US
John Day, M.D., Ph.D., Stanford University, US
Nicholas Johnson, M.D., University of Utah, US
John Kissel, M.D., Ohio State University, US
Jeffrey Statland, M.D., University of Kansas Medical Center, US
S.H. Subramony, M.D., University of Florida, US
Laurie Gutmann, M.D., University of Iowa, US
“PHENO-DM1- Myotonic Dystrophy type 1 (DM1) deep phenotyping to improve delivery of personalized medicine and assist in the planning, design and recruitment of clinical trials”
PI: Hanns Lochmüller, MD
Newcastle University, UK
Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy. The multisystemic phenotype may be highly variable between patients and therefore the selection of appropriate endpoints for therapeutic trials is of great importance for trial readiness. Newcastle University and University College London are working together to deep-phenotype 200-400 DM1 adult patients in the UK and investigate potential biomarkers and skeletal muscle MRI over 9-12 months. The team is currently funded through a UK National Institute for Health Research grant. The on-going study represents an opportunity to leverage the existing funding and data in order to obtain detailed, long-term (24 month) phenotypic data from a large DM1 cohort. Funding from MDF UK, in partnership with MDF US, will extend the study for an additional 18 months, thereby providing extensive natural history data that will be invaluable in design of clinical trials in DM1.
“Development of Magnetic Resonance Imaging as an Endpoint in Myotonic Dystrophy Type 1”
PI: Donovan Lott, PhD
University of Florida, US
Magnetic Resonance Imaging (MRI) has been very useful in examining the muscles of people with different diseases, and it should be important for assessment of people with myotonic dystrophy type 1 (DM1). The goal of this study is to develop MRI of the legs and arms for people with DM1 so that MRI can be used as an endpoint in clinical trials. Specifically, Dr. Lott and team will use MRI to measure different ways the DM1 disease affects muscles and will examine how those measures relate to walking, balance, falls, strength, and arm function.
2015 MDF Grant Recipients
In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2015:
“Inhibiting transcription of CUG/CCUG expanded repeats with small molecules”
PI: Andy Berglund, PhD of the University of Florida
PI: Paul August, PhD of Sanofi
The pharmaceutical company Sanofi and the University of Florida have been awarded a grant the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK to screen for new drugs to treat DM1 and DM2. The University of Florida will be optimizing an assay designed to identify compounds that inhibit the transcription of the repeats in the DM1 and/or DM2 genes, and then will work with Sanofi to conduct a high throughput screen to identify drug candidates. This work builds on a previous discovery by Dr. Berglund and colleagues that the antibiotic actinomycin D can block transcription of CUG repeats at nanomolecular concentrations.
“Assay Development for a Study of Genetic Prevalence in Myotonic Dystrophy”
Nicholas Johnson, PhD
University of Utah, US
Dr. Johnson's research proposal will lead to a better understanding of the prevalence of the disease-causing mutation or premutation in DM1 and DM2 in the general population, specifically in the US where disease prevalence information is lacking. Accurate information regarding how many people in the US have DM1 and DM2 mutations, or are at risk of repeat expansion, will improve service provision, basic research, drug development and policymaking related to DM. In the first phase of this RFA award, Dr. Johnson will develop and validate a cost-effective screening methodology capable of estimating the prevalence of DM1 and DM2 mutations and pre-mutations in the general US population.