FSHD Molecular Characterization

Clinical and Molecular Characterization of Facioscapulohumeral Muscular Dystrophy (FSHD)

To characterize the clinical and molecular phenotype of FSHD.

Study Overview

• Status: Recruiting
• Conditions: Facio-Scapulo-Humeral Dystrophy

Detailed Description

The purpose of this study is to validate alterations in therapeutically relevant biomarkers in muscle tissue from FSHD patients. These biomarkers are responsive to the upregulation of the DUX4 gene and protein, which is the fundamental molecular defect in FSHD. In anticipation of a future clinical trial, the Investigators intend to assess the correlation between the expression of these relevant biomarkers and clinical functional measures. The Investigators will also explore the utility of muscle MRI in identifying regions of muscle suitable for sampling for relevant biomarkers, as MRI-related signal changes have been proposed as an anatomic marker of early FSHD pathology.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Sarah Atkins; Phone Number: 614-355-7686; Email: sarah.atkins@nationwidechildrens.org

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • The Abigail Wexner Research Institute at Nationwide Children's Hospital
      • Contact: Robyn Cunningham; Phone Number: 614-722-2599; Email: robyn.cunningham@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects 13 years or older with facioscapulohumeral muscular dystrophy (FSHD).

Description

Inclusion Criteria:

• 13 years or older
• Genetically proven FSHD1 or FSHD2 as determined by the investigators

Exclusion Criteria:

• Inability to complete an MRI scan (Adults only).
• Other medical or cognitive issues that, in the opinion of the examiner, preclude accurate functional assessment.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of Biomarkers	To validate alterations in therapeutically relevant biomarkers in muscle tissue from FSHD participants. Each participant will provide data at a single timepoint. The data in totality will be reviewed upon study completion.	Through study completed, anticipated to be 4 years.

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Investigators: Principal Investigator: Kevin Flanigan, MD, Nationwide Children's Hospital

Publications and helpful links

General Publications

• Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486. doi: 10.1093/hmg/ddy364.
• Amini Chermahini G, Rashnonejad A, Harper SQ. RNAscope in situ hybridization-based method for detecting DUX4 RNA expression in vitro. RNA. 2019 Sep;25(9):1211-1217. doi: 10.1261/rna.070177.118. Epub 2019 Jun 17.
• Jones TI, Chen JC, Rahimov F, Homma S, Arashiro P, Beermann ML, King OD, Miller JB, Kunkel LM, Emerson CP Jr, Wagner KR, Jones PL. Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: evidence for disease modifiers and a quantitative model of pathogenesis. Hum Mol Genet. 2012 Oct 15;21(20):4419-30. doi: 10.1093/hmg/dds284. Epub 2012 Jul 13.
• Snider L, Asawachaicharn A, Tyler AE, Geng LN, Petek LM, Maves L, Miller DG, Lemmers RJ, Winokur ST, Tawil R, van der Maarel SM, Filippova GN, Tapscott SJ. RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of facioscapulohumeral dystrophy. Hum Mol Genet. 2009 Jul 1;18(13):2414-30. doi: 10.1093/hmg/ddp180. Epub 2009 Apr 9.
• Yao Z, Snider L, Balog J, Lemmers RJ, Van Der Maarel SM, Tawil R, Tapscott SJ. DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle. Hum Mol Genet. 2014 Oct 15;23(20):5342-52. doi: 10.1093/hmg/ddu251. Epub 2014 May 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): March 5, 2025
• Study Completion (Estimated): March 5, 2026

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: FSHD
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Facioscapulohumeral
• Other Study ID Numbers: STUDY00001521

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will be willing to share de-identified data following the execution of a Data Use Agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No