The Myotonic Dystrophy Foundation made the following grants in 2024:
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.
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.
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.