Journal article
Establishing biomarkers and clinical endpoints in myotonic dystrophy type 1 (END-DM1): Protocol of an international natural history study
PloS one, Vol.20(12), e0331163
2025
DOI: 10.1371/journal.pone.0331163
PMCID: PMC12697934
PMID: 41379803
Abstract
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited multi-system disorder that affects skeletal muscles but also many other organ systems. Molecular targets have been identified and targeted therapies are being developed and tested in first-in-human clinical trials. However, insufficient knowledge of the phenotypic heterogeneity and natural course of the disease, together with a lack of reliable biomarkers, complicate the design of clinical trials.
The main objectives of this study are to 1) characterize the phenotypic heterogeneity and disease progression of DM1 in a large cohort; 2) identify baseline characteristics that predict subsequent progression; 3) validate RNA biomarkers of disease severity. This is a prospective, multi-site observational study with a follow-up period of 24 months including approximately 700 adult DM1 patients. Visits will occur at baseline, and months 12 and 24. All patients will undergo strength testing, myotonia assessment, a battery of functional outcome assessments, spirometry, and complete various questionnaires and cognitive tests. Blood and urine samples will be taken at each visit for biomarker studies. A subset of 60 patients will undergo a muscle biopsy at baseline and at an additional 3-month visit. The sensitivity to disease progression and minimally clinically important differences will be determined for the various clinical outcome measures. Associations between baseline patient characteristics and the rate of disease progression will be evaluated.
The results of this large international study on DM1 will contribute to optimizing clinical trial design. Both data and biological samples will be collected for future research as well.
Clinicaltrials.gov NCT03981575.
Details
- Title: Subtitle
- Establishing biomarkers and clinical endpoints in myotonic dystrophy type 1 (END-DM1): Protocol of an international natural history study
- Creators
- Karlien Mul - Radboud University Medical CenterKate Eichinger - University of Rochester Medical CenterMan Hung - Virginia Commonwealth UniversityValeria A Sansone - Centro Clinico NemoCynthia Gagnon - Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-JeanSub Subramony - University of FloridaRichard H Roxburgh - University of AucklandJohanna Hamel - University of Rochester Medical CenterJeffrey M Statland - University of Kansas Medical CenterBakri Elsheikh - The Ohio State University Wexner Medical CenterChris Turner - University College LondonJacinda Sampson - Stanford UniversityThomas Ragole - University of Colorado Anschutz Medical CampusEmma Matthews - St George’s University Hospitals NHS Foundation TrustBenedikt Schoser - Friedrich Baur StiftungAndrea Swenson - University of IowaChamindra Laverty - University of California San DiegoPerry Shieh - University of California, Los AngelesEricka P Greene - Houston MethodistMasanori Takahashi - The University of OsakaMatthew Wicklund - The University of Texas Health Science Center at HoustonJeanne Dekdebrun - University of Rochester Medical CenterJennifer Raymond - Virginia Commonwealth UniversityErin DeSpain - Virginia Commonwealth UniversityCharles A Thornton - Virginia Commonwealth UniversityNicholas E Johnson - Virginia Commonwealth UniversityMyotonic Dystrophy Clinical Research Network
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.20(12), e0331163
- DOI
- 10.1371/journal.pone.0331163
- PMID
- 41379803
- PMCID
- PMC12697934
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- PUBLIC LIBRARY SCIENCE
- Grant note
- Vertex Pharmaceuticals: PO 7571439 Takeda Pharmaceuticals U.S.A.: FP00019070 Dyne Therapeutics: FP00011118 Pfizer: FP00019023 Sanofi Genzyme: E005477258 Arthex Biotech: FP00021773 U.S. Food and Drug Administration: 7R01FD006071-02 and 5R01FD006071-05 PepGen Inc: FP00019245 Myotonic Dystrophy Foundation: DMCRN 001 Avidity Biosciences: FP00013850
NEJ acquired funding for the study from the Food and Drug Administration (FDA; grant numbers 7R01FD006071-02 and 5R01FD006071-05; https://www.fda.gov), the Myotonic Dystrophy Foundation (grant number DMCRN 001; https://www.myotonic.org), Avidity Biosciences (grant number FP00013850; https://aviditybiosciences.com), Dyne Therapeutics (grant number FP00011118; https://www.dyne-tx.com), Vertex Pharmaceuticals Incorporated (grant number PO 7571439; https://www.vrtx.com), PepGen Inc. (grant number FP00019245; https://www.pepgen.com), Sanofi (grant number E005477258; https://www.sanofi.com), Takeda Pharmaceutical Company Limited (grant number FP00019070; https://www.takeda.com), Pfizer Inc. (grant number FP00019023; https://www.pfizer.com), and ArthEx Biotech (grant number FP00021773; https://arthexbiotech.com). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Language
- English
- Date published
- 2025
- Academic Unit
- Neurology
- Record Identifier
- 9985091815402771
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