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.