Clinical trial NCT06096441: FSHD Molecular Characterization
Official title: Clinical and Molecular Characterization of Facioscapulohumeral Muscular Dystrophy (FSHD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Facio-Scapulo-Humeral Dystrophy
Keywords: FSHD
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 25
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects 13 years or older with facioscapulohumeral muscular dystrophy (FSHD).

Brief summary: To characterize the clinical and molecular phenotype of FSHD.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Validation of Biomarkers
timeFrame: Through study completed, anticipated to be 4 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Abigail Wexner Research Institute at Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: Kevin Flanigan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.