The Myotonic Dystrophy Foundation made the following grants in 2024:

2024 MDF Pilot Grant Recipients

Joel R. Chamberlain, Ph.D. 
Research Associate Professor
University of Washington, Seattle, WA, US

Project: Efficacy Testing of Cell-Derived Nanovesicle Delivery of Small Interfering RNAs for Treatment of DM1

Dr. Chamberlain is exploring a novel approach to treat DM1 by using natural cell-derived vesicles to deliver drugs that can destroy toxic RNA structures in muscles. If successful, this could lead to a new, non-invasive treatment that targets the root cause of DM1.

Paloma Gonzalez Perez, M.D., Ph.D.  
Neuromuscular Attending
Massachusetts General Hospital, Boston, MA, US

Project: Investigating Benefits of a Physical Therapist-Guided Exercise Program in Myotonic Dystrophy Type 2

Dr. Gonzalez Perez is testing the effectiveness of a simple, guided exercise program designed to improve motor function and reduce pain in DM2 patients. Her study will examine the long-term benefits of exercise under physical therapist supervision, with the goal of making this program accessible to more DM2 patients.

Emma Matthews, FRCP  
Reader of Neurology and Consultant Neurologist 
St George's, University of London, UK

Project: Exploring Transcriptional Dysregulation of Lipid Metabolism Genes in DM1

Dr. Matthews aims to uncover why DM1 patients are more prone to abnormal lipid profiles (dyslipidemia). By comparing lipid metabolism genes in DM1 patients with and without dyslipidemia, her study could lead to better treatment guidelines and new therapies for managing this condition.

Belinda Pinto, Ph.D.  
Research Assistant Scientist
University of Florida, Gainesville, FL, US

Project: Investigating the Contribution of Circadian Disruption to Hypersomnolence in Myotonic Dystrophy 

Dr. Pinto is studying how disruptions in the circadian system contribute to excessive daytime sleepiness in DM1 patients. Using animal models, she seeks to understand the molecular causes of hypersomnia and pave the way for future therapeutic developments.

2024 MDF Early Career Researchers

Johanna Hamel, MD
Assistant Professor
University of Rochester, New York, US

DM1 exhibits considerable variability, even within families. Symptoms can emerge at any life stage, with earlier onset often indicating a more severe form. The underlying CTG repeat mutation, measured in blood cells, ranges widely from >50 to >1000 repeats. Initially, it was believed that this repeat length reliably predicted symptom timing and severity, but recent research challenges this, sparking ongoing debate in the medical community. This uncertainty complicates the work of healthcare professionals managing diverse symptoms and genetic factors, especially in clinical trials for new treatments. Dr. Hamel's pilot study demonstrated the feasibility of remote assessments for DM1 via video conferencing and toolkits. Her larger study “Remote Assessments in Myotonic Dystrophy” aims to assess the role of repeat length in disease onset and severity, reaching individuals across the country, including those underrepresented in research. This proposal aims to expand the remote research platform, enhance community involvement, and lay the groundwork for Genome-wide Association Studies. By exploring residual variance in symptom onset not explained by repeat length, the study aims to identify genetic modifiers. Integrating genetic and clinical data into patient registries improves them as valuable research tools, streamlining patient recruitment and categorization for future therapeutic trials, ultimately enhancing trial effectiveness and reducing patient burden. Click here to read more about Dr. Johanna Hamel.

Tahereh Kamali, PhD
Postdoctoral Research Fellow
Stanford University School of Medicine, California, USA

DM affects various organ systems, including the Central Nervous System (CNS). Despite being a primary concern for patients, understanding CNS symptoms remains limited due to the complex nature of CNS function and a lack of clinical data. The scarcity of complete clinical data poses a significant challenge in DM research, hindering robust statistical analyses and the effectiveness of clinical trials. This limitation makes it challenging to identify reliable biomarkers and validate outcome measures for targeted therapies. Despite efforts to share data between healthcare institutions, the rarity of DM restricts the number of patients available for study, impeding advancements in researchers' understanding and treatment development. In recent years, Dr. Tarareh Kamali's team made strides by creating an artificial intelligence (AI) model capable of identifying specific CNS changes indicative of DM progression. Their next step involves enhancing this AI model, addressing data scarcity by creating synthetic yet realistic CNS data and incorporating real-world patient data. This innovative project “Utilizing Generative AI to Expand Clinical Data for DM Studies and Treatment Efficacy Planning” aims to revolutionize DM research, facilitating more accurate diagnoses and personalized treatments. By deepening our understanding of how DM affects the CNS, the research seeks transformative strategies that can alter the disease's course, offering hope and improved quality of life for those affected. Leveraging cutting-edge technology, this project brings us closer to unraveling the complexities of DM, paving the way for effective treatment strategies and a healthier future for individuals with this condition. Click here to read more about Dr. Tahereh Kamali.

High Priority, Short-Term Project Award

These grants are for $50,000, over one year, for Early Career applications designated as high priority by the MDF Board. The funding provides interim research support designed to enable the Principal Investigator to gather additional data.

Kristina Kelly, DPT
Assistant Research Professor
University of Missouri-Columbia, Missouri, US

Fatigue poses a significant yet underexplored challenge for individuals with DM1. Understanding the underlying biology of fatigue is crucial for developing effective interventions. One facet of fatigue is motor fatigability, characterized by a measurable decline in physical performance during a specific task. To investigate, they will examine the nervous system's role, a component often influenced by DM1. The study “Neural Mechanisms of Motor Fatigability in Myotonic Dystrophy Type 1” involves individuals with DM1 and healthy controls, evaluating motor fatigability using clinical measures. In the first phase, we will analyze nervous system activity in the quadriceps muscles, comparing those with DM1 experiencing motor fatigability, those without, and healthy controls. Anticipated findings include reduced nervous system activity in those with motor fatigability. The second phase assesses nervous system activity post-30 minutes of cycling exercise, aiming to understand differences among participants. They hypothesize distinctive responses in the nervous systems of those with DM1 and motor fatigability. While exercise benefits individuals with DM1, understanding its impact on fatigue is essential for personalized recommendations. Cycling, a safe and feasible exercise, was chosen to broaden the study's applicability. By investigating real-world movements resembling those causing fatigability, they aim to provide insights applicable to a wider DM1 population. This study marks a crucial initial exploration into DM1 fatigue biology, laying the groundwork for future interventions to enhance the lives of individuals with DM1.

Lukasz Sznajder, PhD, MSc
Assistant Research Professor
University of Nevada, Las Vegas, US

DM2 has garnered less attention than DM1, lacking approved treatments or clinical trials. The uncertainty persists in applying DM1 therapeutic strategies to DM2. Tailoring approaches to the DM2 molecular mechanism is crucial. Despite commonalities, DM2's mechanism seems more intricate. Evidence points to expanded CCUG RNA repeats' toxicity as the primary cause. The prior research unveiled that these repeats persist in an improperly spliced mRNA exported to the cytoplasm, a vital revelation. Yet, confirmation that this mRNA constitutes a pathogenic molecule in DM2 is pending. This project “Delineating pathogenic RNA species in myotonic dystrophy type 2” aims to validate the hypothesis that mRNA with retained CCUG repeats is a key pathogenic factor in DM2, driving characteristic molecular changes. Additionally, they will develop preventative therapeutic strategies. Leveraging DM2-derived cell lines, and tissues, and employing bioinformatics and molecular biology tools will help achieve these objectives. Identifying primary pathogenic molecules will enhance the understanding of DM2 and lay the groundwork for therapeutic development.

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. Click here to read more about Dr. Dylan Farnsworth.

Matteo Garibaldi, MD, PhD
Assistant Professor
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. Click here to ready more about Dr. Matteo Garibaldi.

Melissa Hale, PhD
Assistant Professor
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. Click here to read more about Dr. Melissa Hale.

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.

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.

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.

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.

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.

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.