Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY/ABSTRACT Myotonic dystrophy (dystrophia myotonica or DM) is the most common muscular dystrophy in adults (prevalence is 1/8,000) and an autosomal dominant multisystem disease caused by a CTG trinucleotide expansion in DMPK gene (DM type 1) or CCTG tetranucleotide expansion in CNBP gene (DM type 2). Such DNA expansions are responsible for the presence of toxic RNA molecules. Promising therapies are in current development to target these RNA transcripts; however, disease biomarkers to monitor disease activity and patient’s response to upcoming treatments are lacking. The proposed research focuses on identifying reliable and non-invasive biomarkers that serve to monitor the slow progression of DM muscle disease and that can be later used to also monitor response to upcoming treatments. This project not only addresses the need for muscle biomarkers in DM type 1 but also in DM type 2, that although less frequent, it is probably underdiagnosed. The applicant’s research strategy aims at investigating skeletal muscle MRI and ultrasound, and electrical impedance myography as monitoring disease biomarkers. The candidate’s research environment is ideal for the proposed project. The Massachusetts General Hospital (MGH) and Harvard Medical School provide an enriching and motivating academic atmosphere for trainees who have the opportunity to attend high-quality courses/lectures, collaborate with expert scientists and clinicians in the field of neuromuscular disorders and skeletal muscle imaging. The candidate’s mentoring team is composed by Dr. Thurman Wheeler and Dr. Seward Rutkove. Dr. Wheeler has been investigating DM for almost two decades by using in vitro and animal models of the disease, and more recently also disease biomarkers in patients’ biofluids. He has significantly contributed to advance the understanding of DM and he has become a renowned researcher in the field as shown in his numerous high-impact factor publications. Dr. Rutkove is a neuromuscular specialist with expertise on skeletal muscle ultrasound and electrical impedance myography, and with a successful clinical research career in the design and development of new technologies to better characterize neuromuscular diseases. As collaborator and consultant, Dr. Martin Torriani who directs the MGH Musculoskeletal Imaging Core and is an expert on skeletal muscle MRI. The advisory team will also contribute with expertise in applied computational methods and biostatistics (Dr. Hang Lee), and high-quality translational research in neuromuscular diseases and readiness for biomarker application into future clinical trials (Dr. Basil Darras and Dr. Sabrina Paganoni). The candidate’s training plan includes career development lectures (i.e Training in Responsible Conduct of Research), Harvard Catalyst courses (i.e Certificate in Applied Biostatistics) and attendance to scientific meetings (i.e Myotonic Dystrophy Foundation and Muscle Study Group). Candidate’s career goal is to transition towards an independent clinician-scientist position in the field of neuromuscular diseases with main focus on muscular dystrophies and patient-oriented research.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).