Abstract Details

Title A Prospective Longitudinal Observational Study in Myotonic Dystrophy Type One: From Clinical Outcomes to Trial Design

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-003

Objective

The END-DM1 study is an international prospective longitudinal study involving adult with DM1 to establish biomarkers and clinical endpoints using harmonized protocols and procedures. Here we seek to determine the burden of disease and select endpoints for clinical trials.

Background Myotonic dystrophy type 1 (DM1) is among the most variable of diseases, with a wide range of disease burden. Large cohorts are required to assess the variable disease burden to determine appropriate endpoints for clinical trials and to standardize trial site processes.

Design/Methods

Individuals with DM1 who were older than 18 were enrolled in a 24-month observational study. Measures of cognition, quantitative muscle strength, motor function (e.g., 10 MWT, 6 MWT), myotonia, cardiac arrhythmias, pulmonary function, and quality of life were collected. The medical history and age of onset were collected at baseline. A subset of the cohort had muscle biopsies to assess the degree of RNA mis-splicing.

Results 700 adults with DM1 were enrolled and the baseline results are presented here. The mean age of the participants was 44 years old, and the mean age of onset was 25. Of the participants, 0.33% were non-ambulatory. Strong associations were identified between measures of muscle strength and motor function, while weak associations were identified with myotonia. The cohort had a wide range of performance on the cogstate, a measure of cognition, with some performing above average. Approximately 1/3 of the cohort had arrhythmias identified on the electrocardiogram.

Conclusions The Myotonic Dystrophy Clinical Research Network (DMCRN) proves to be a valid framework to collect clinical and demographic data from a large international cohort of adults with DM1. It allows to compare differences between cohorts and to identify potential fast progressors and most sensitive outcomes that may need to be accounted for in the design of future clinical trials.

Authors/Disclosures
Valeria A. Sansone, MD (The NEMO Clinical Center - Neurorehabilitation Unit, University of Milan) PRESENTER	Dr. Sansone has nothing to disclose.
Carola Ferrari Aggradi (The NEMO Clinical Center - Neurorehabilitation Unit, University of Milan)	No disclosure on file
Andrea Lizio, MS in Biostatistics	Dr. Lizio has nothing to disclose.
Michela Nani (The NEMO Clinical Center - Neurorehabilitation Unit, University of Milan)	No disclosure on file
Jeanne Dekdebrun	Ms. Dekdebrun has received personal compensation for serving as an employee of Avidity. Ms. Dekdebrun has received personal compensation for serving as an employee of Arthex. Ms. Dekdebrun has received personal compensation for serving as an employee of Dyne. Ms. Dekdebrun has received personal compensation for serving as an employee of Lupin. Ms. Dekdebrun has received personal compensation for serving as an employee of PepGen. Ms. Dekdebrun has received personal compensation for serving as an employee of Sanofi. Ms. Dekdebrun has received personal compensation for serving as an employee of Vertex.
Katy Eichinger, PhD, PT, DPT, NCS (University of Rochester)	Dr. Eichinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Fulcrum. Dr. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avidity. Dr. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for DyneTherapeutic. Dr. Eichinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TRiNDS. The institution of Dr. Eichinger has received research support from Charcot Marie Tooth Association. The institution of Dr. Eichinger has received research support from Muscular Dystrophy Association. Dr. Eichinger has received intellectual property interests from a discovery or technology relating to health care.
Cynthia Gagnon (Sherbrooke University)	No disclosure on file
S H. Subramony, MBBS, FAAN (University of Florida)	Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lupin. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fallonmedica. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Subramony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fulcrum. The institution of Dr. Subramony has received research support from Reata. The institution of Dr. Subramony has received research support from Retrotope. The institution of Dr. Subramony has received research support from Acceleron. The institution of Dr. Subramony has received research support from Biohaven. The institution of Dr. Subramony has received research support from Pharnext. The institution of Dr. Subramony has received research support from Fulcrum. The institution of Dr. Subramony has received research support from National Ataxia Foundation. The institution of Dr. Subramony has received research support from Friedreich Ataxia Research Alliance. The institution of Dr. Subramony has received research support from Muscular Dystrophy Association. The institution of Dr. Subramony has received research support from Univ of Rochester, MDA. The institution of Dr. Subramony has received research support from Virginia Commonwealth Univ (FDA, Wyck Foundation)). The institution of Dr. Subramony has received research support from Children's Hospital, Philadelphia (FDA). The institution of Dr. Subramony has received research support from Houston Methodist (NIH). The institution of Dr. Subramony has received research support from NIHR01 AR076060-01A1 . The institution of Dr. Subramony has received research support from NIH2R42HD089804-04 . The institution of Dr. Subramony has received research support from NIH R01 AR056973 . The institution of Dr. Subramony has received research support from FSHD Society. The institution of Dr. Subramony has received research support from AAVANTI BIO. The institution of Dr. Subramony has received research support from COHAV FL State Dept of Health. The institution of Dr. Subramony has received research support from Avidity. The institution of Dr. Subramony has received research support from PTC. The institution of Dr. Subramony has received research support from Biohaven. The institution of Dr. Subramony has received research support from Fulcrum. The institution of Dr. Subramony has received research support from Vertex. The institution of Dr. Subramony has received research support from Arthrex.
Richard Roxburgh, MD, PhD, FRACP (Auckland Hospital)	Dr. Roxburgh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Roxburgh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CHDI. The institution of Dr. Roxburgh has received research support from Biogen. The institution of Dr. Roxburgh has received research support from Roche.
Johanna Hamel, MD (University of Rochester, Neurology)	Dr. Hamel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals.
Jeffrey Statland, MD (University of Kansas Medical Center)	Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ML Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epic Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Armatus . Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kate Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vita Therapeutics. Dr. Statland has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity . Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum Therapeutics. Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex . The institution of Dr. Statland has received research support from NIH. The institution of Dr. Statland has received research support from FSHD Society. The institution of Dr. Statland has received research support from Friends of FSH Research. The institution of Dr. Statland has received research support from FSHD Canada. The institution of Dr. Statland has received research support from MDA.
Karlien Mul	The institution of Karlien Mul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Biosciences.
Baziel G. van Engelen, MD, PhD, MA (Radboud University Nijmegen Medical Centre)	The institution of Dr. van Engelen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum . The institution of Dr. van Engelen has received research support from Stichting Spieren voor Spieren. The institution of Dr. van Engelen has received research support from Prinses Beatrix Fonds. The institution of Dr. van Engelen has received research support from Dutch FSHD society. Dr. van Engelen has received intellectual property interests from a discovery or technology relating to health care.
Bakri Elsheikh, MD, FAAN (The Ohio State University Wexner Medical Center)	Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Dr. Elsheikh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argnex . The institution of Dr. Elsheikh has received research support from Biogen. The institution of Dr. Elsheikh has received research support from Cure SMA.
William D. Arnold, MD	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for La Hoffmann Roche. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadent Therapeutics . Dr. Arnold has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Arnold has received research support from NIH. The institution of Dr. Arnold has received research support from NMD Pharma. The institution of Dr. Arnold has received research support from Gilead Sciences. The institution of Dr. Arnold has received research support from CureSMA. Dr. Arnold has received intellectual property interests from a discovery or technology relating to health care.
Chris Turner, MD, PhD	Dr. Turner has received personal compensation for serving as an employee of Vertex Pharmaceuticals . Dr. Turner has received personal compensation for serving as an employee of Dyne Therapeutics . Dr. Turner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmacueticals. Dr. Turner has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Turner Enterprises . The institution of Dr. Turner has received research support from Lupin .
Benedikt Schoser	Benedikt Schoser has received personal compensation for serving as an employee of Alexion. Benedikt Schoser has received personal compensation for serving as an employee of Argenx. Benedikt Schoser has received personal compensation for serving as an employee of Amicus. Benedikt Schoser has received personal compensation for serving as an employee of Astellas. Benedikt Schoser has received personal compensation for serving as an employee of Denali. Benedikt Schoser has received personal compensation for serving as an employee of Avidity . Benedikt Schoser has received personal compensation for serving as an employee of Sanofi. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Taysha. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astellas. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Encoded. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kedrion.
Thomas E. Ragole, MD	The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. The institution of Dr. Ragole has received research support from Alexion Pharmaceuticals.
Emma Matthews, MD (MRC Centre for Neuromuscular Diseases)	Dr. Matthews has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lupin Pharmaceuticals. The institution of Dr. Matthews has received research support from Myotonic Dystrophy Foundation.
Jacinda B. Sampson, MD, PhD	Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viking Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Sampson has received research support from Marigold Foundation. Dr. Sampson has a non-compensated relationship as a Scientific Advisory Committee with Myotonic Dystrophy Foundation that is relevant to AAN interests or activities.
Massanori Takahashi, MD, PhD (Clinical Neurophysiology, Osaka University)	Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Japan Clinical Research Operations. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nippon Shinyaku. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharmaceutical. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for argenx. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Japan. Dr. Takahashi has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Myotonic Dystrophy Patients' Group of Japan. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson & Johnson.
Matthew P. Wicklund, MD, FAAN (UT Health San Antonio)	Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics. Dr. Wicklund has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Wicklund has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Wicklund has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Spark Therapeutics. Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ultragenyx. Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmaceuticals. The institution of Dr. Wicklund has received research support from Orphazyme. The institution of Dr. Wicklund has received research support from Muscular Dystrophy Association. The institution of Dr. Wicklund has received research support from Coalition to Cure Calpain 3. The institution of Dr. Wicklund has received research support from Sarepta Therapeutics. The institution of Dr. Wicklund has received research support from ML Bio. The institution of Dr. Wicklund has received research support from Alexion. The institution of Dr. Wicklund has received research support from Acceleron. The institution of Dr. Wicklund has received research support from Edgewise. The institution of Dr. Wicklund has received research support from Fulcrum. The institution of Dr. Wicklund has received research support from Roche-Genentech. The institution of Dr. Wicklund has received research support from Avidity. Dr. Wicklund has received research support from Harmony Bioscience.
Andrea J. Swenson, MD (University of Iowa Hospitals and Clinics)	An immediate family member of Dr. Swenson has received personal compensation for serving as an employee of IDT. Dr. Swenson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. An immediate family member of Dr. Swenson has received stock or an ownership interest from IDT.
Chamindra G. Laverty, MD (UC San Diego)	The institution of Dr. Laverty has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sarepta . Dr. Laverty has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Laverty has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Laverty has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Solid Biosciences. Dr. Laverty has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. The institution of Dr. Laverty has received research support from Sarepta. The institution of Dr. Laverty has received research support from Novartis Gene Therapies. The institution of Dr. Laverty has received research support from Italfarmaco. The institution of Dr. Laverty has received research support from Fibrogen. The institution of Dr. Laverty has received research support from Avidity. The institution of Dr. Laverty has received research support from Dyne.
Perry Shieh, MD, PhD, FAAN (UCLA)	Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Catalyst.
Ericka P. Greene, MD, FAAN (Methodist Hospital)	Dr. Greene has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis . Dr. Greene has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for ABPN. Dr. Greene has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Abraham & Watkins Texas Law Firm. The institution of Dr. Greene has received research support from National Science Foundaton .
Man Hung (Roseman University)	No disclosure on file
Ruby Langeslay, MPH	Ms. Langeslay has nothing to disclose.
Jennifer G. Raymond	Mrs. Raymond has nothing to disclose.
Charles A. Thornton, MD, FAAN (University of Rochester Medical Center)	Dr. Thornton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Thornton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Thornton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis. Dr. Thornton has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne. Dr. Thornton has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pepgen. The institution of Dr. Thornton has received research support from Marigold Foundation. The institution of Dr. Thornton has received research support from NIH. The institution of Dr. Thornton has received research support from Muscular Dystrophy Association . The institution of Dr. Thornton has received research support from Dyne. The institution of Dr. Thornton has received research support from Avidity. The institution of Dr. Thornton has received research support from Ionis. Dr. Thornton has received intellectual property interests from a discovery or technology relating to health care.
Nicholas E. Johnson, MD, FAAN (Virginia Commonwealth University)	Dr. Johnson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sarepta Therapuetics. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharma. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Johnson has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Arthex. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Juvena. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rgenta. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AskBio. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Johnson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Evolyra Therapeutics . Dr. Johnson has stock in Angle Therapeutics. Dr. Johnson has stock in Juvena Therapeutics. Dr. Johnson has stock in Evolyra Therapeutics. The institution of Dr. Johnson has received research support from Novartis. The institution of Dr. Johnson has received research support from Takeda . The institution of Dr. Johnson has received research support from AMO Pharma. The institution of Dr. Johnson has received research support from Sarepta. The institution of Dr. Johnson has received research support from Dyne Therapeutics. The institution of Dr. Johnson has received research support from AskBio. The institution of Dr. Johnson has received research support from Pepgen. The institution of Dr. Johnson has received research support from ML Bio. The institution of Dr. Johnson has received research support from Vertex. The institution of Dr. Johnson has received research support from Arthex. The institution of Dr. Johnson has received research support from Avidity Biosciences. The institution of Dr. Johnson has received research support from Edgewise. Dr. Johnson has received intellectual property interests from a discovery or technology relating to health care.

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