EIM Phase Angle as a Candidate Biomarker of Muscle Function in DM1 Patients (P3-8.005)

Objective: To evaluate electrical impedance myography as a non-invasive indicator of muscle disease status in DM1 patients. Background: Myotonic dystrophy type 1 (DM1) is a multisystem neurogenetic disorder characterized by delayed relaxation and progressive wasting of muscle, among other symptoms. Clinical trials currently rely on invasive measures of therapeutic response, such as repeat muscle biopsies. Electrical impedance myography (EIM) is a painless, non-invasive technique that uses low-intensity current to assess muscle fiber composition and architecture through the skin. Studies in other neuromuscular disorders and in DM1 mice indicate that EIM may provide valuable metrics of muscle disease status, progression, and response to therapy. However, the usefulness of EIM in DM1 patients is unknown. Design/Methods: Using the Myolex mScan, we applied alternating current at 41 frequencies (1 – 10,000 kHz) and measured the resulting voltage in 7 muscle groups of DM1 (N = 21) and unaffected (N = 8) subjects. From the resistance and reactance, we calculated the phase angle—the time shift of electric current as it passes through muscle. All subjects also underwent quantitative muscle function testing. A subset of 14 DM1 subjects were re-evaluated at 6-to-8 months. Results: Mean phase angle at 100 kHz is significantly reduced in the wrist flexor, wrist extensor, tibialis anterior, and gastrocnemius muscles of DM1 vs unaffected subjects. Phase angle correlates with strength in the biceps, triceps, wrist flexors, wrist extensors, gastrocnemius, and tibialis anterior (r 0.61 – 0.70; P < 0.0001). Tibialis anterior and gastrocnemius phase angles correlate with 6-minute-walk distance (r 0.68 and 0.64; P 0.0007 and 0.002) and 10-meter-walk time (r −0.60 and −0.56; P 0.008 and 0.004). Phase angle values are reproducible from side-to-side and between first and second visits. Conclusions: EIM phase angle is a candidate biomarker of disease status in DM1 muscle tissue. Disclosure: Mr. Conquest has nothing to disclose. Mr. McKee has nothing to disclose. The institution of Ms. Cornforth has received research support from NIH. The institution of Ms. Cornforth has received research support from DOD. Mr. Sizemore has nothing to disclose. Elise Townsend has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Aspa Therapeutics . The institution of Elise Townsend has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Elise Townsend has stock in Biogen. The institution of Elise Townsend has received research support from NTSAD. The institution of Elise Townsend has received research support from DOD. Dr. Rutkove has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Myolex, Inc. Dr. Rutkove has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neuorlogy . Dr. Rutkove has received stock or an ownership interest from Myolex, inc. Dr. Rutkove has received stock or an ownership interest from Haystack Diagnostics. The institution of Dr. Rutkove has received research support from NIH. The institution of Dr. Rutkove has received research support from NASA. The institution of Dr. Rutkove has received research support from Blavatnik Family Foundation. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with NIH. Dr. Wheeler has nothing to disclose.