Abstract Details

Title Quantitative muscle analysis in FSHD using Whole-Body MRI: Composite Muscle Measurements for Cross-Sectional Analysis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 11-001

Background Functional assessments show limited sensitivity in detecting slowing or arrest of disease progression in FSHD. MRI can potentially detect pathological changes in muscle prior to changes in clinical outcome assessments (COA).
Fulcrum is developing losmapimod, a small molecule inhibitor of p38 α/β MAPK, to reduce DUX4 expression with the intent to decrease/arrest replacement of muscle by fat.

Objective Develop an optimized whole-body MRI protocol and composite analysis that correlates with clinical outcome assessments in Facioscapulohumeral Muscular Dystrophy (FSHD).

Design/Methods This was a prospective, observational, multicenter study. Seventeen adults aged 18 to 65 with FSHD1 enrolled at 6 sites, imaged at baseline and 4 to 12 weeks later. Volumetric analysis of 36 muscles included the shoulder girdle and upper arm (upper extremity (UE)), torso, and lower extremities (LE). Muscles were identified by an automated atlas-based segmentation and manually verified. Composite scores were generated for muscles associated with COAs including LE for timed up and go (TUG), UE/LE and torso for FSHD-TUG, and UE and trunk muscles for reachable workspace (RWS). MRI endpoint measures included muscle fat fraction (MFF), muscle fat infiltration (MFI) and lean muscle volume (LMV).

Results Total LMV (Pearson’s r=0.9984), MFI (r=0.9845) and MFF (r=0.9918) showed strong correlations between the two timepoints. The composite total MFF and MFI (MFF_tot and MFI_tot) for the LE muscles (10 total) correlated with TUG, 0.72 and 0.83 respectively; UE/LE and trunk muscles (36 total) for FSHD-TUG, 0.73 in both measures and composite total MFF for the UE and trunk muscles (28 total) with RWS (left arm: r=-0.71, r=-0.53; right arm: r=-0.61, r=-0.65).

Conclusions There was strong cross-sectional correlation between whole-body MRI- composite measurements and COAs. MRI measurements can potentially provide important information about disease severity and progression as it correlates with FSHD relevant clinical endpoints.

Authors/Disclosures
PRESENTER	No disclosure on file
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Alrabi Tawil, MD, FAAN (University of Rochester Medical Center)	Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DYNE Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead Pharma. Dr. Tawil 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. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acceleron Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharma. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for miRecule. The institution of Dr. Tawil has received research support from Friends of FSH Research. The institution of Dr. Tawil has received research support from FSH Society. The institution of Dr. Tawil has received research support from NIH. The institution of Dr. Tawil has received research support from Fulcrum. Dr. Tawil has received intellectual property interests from a discovery or technology relating to health care. Dr. Tawil has received publishing royalties from a publication relating to health care.
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 $10,000-$49,999 for serving as a Consultant for Roche. Dr. Eichinger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FSHD Society. The institution of Dr. Eichinger has received research support from Charcot Marie Tooth Association.
Leo H. Wang, MD, PhD, FAAN (University of Washington)	Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AskBio. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum Therapeutics. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Wang has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. The institution of Dr. Wang has received research support from National Institute of Health. Dr. Wang has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with US Government.
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.
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 $10,000-$49,999 for serving as a Consultant for Facio. 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.
Diego Cadavid, MD, FAAN (Verge Genomics)	Dr. Cadavid has received personal compensation for serving as an employee of X4 Pharma. Dr. Cadavid has received personal compensation for serving as an employee of Fulcrum Therapeutics. Dr. Cadavid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arvinas. Dr. Cadavid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. Dr. Cadavid has received stock or an ownership interest from X4 Pharma. Dr. Cadavid has received stock or an ownership interest from Fulcrum Therapeutics.
	No disclosure on file
	No disclosure on file
Jay Han, MD (University of California Davis)	No disclosure on file
Maya N. Hatch, PhD (UC Irvine School of Medicine)	Maya Hatch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bioniks. Maya Hatch has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum. The institution of Maya Hatch has received research support from Fulcrum Therapeutics.
Michelle L. Mellion, MD	Dr. Mellion has received personal compensation for serving as an employee of PepGen. Dr. Mellion has stock in PepGen.