188PBilateral analysis of upper limb endpoints in ambulant and non-ambulant DMD patients.

Abstract

In Duchenne muscular dystrophy (DMD), systemic therapeutical approaches face challenges in tissue exposure. Intramuscular (IM) dosing may increase tissue concentrations, limit systemic adverse effects, and be relevant to more advanced stages of the disease, especially when targeting the upper limb. We compared disease progression between the dominant and non-dominant arm in DMD to explore the possibilities of clinical trials using a self-controlled design in IM interventions. PUL2.0 total score, isometric strength for shoulder abduction, elbow flexion, elbow extension and wrist dorsiflexion using MicroFET2, isokinetic strength for elbow flexion and extension using Biodex pro 4 and handgrip strength using MyoGrip were assessed in the dominant and non-dominant upper limb at baseline and 12 months. Upper arm extensor and flexor muscle fat fractions were assessed with quantitative MRI. Wilcoxon signed rank test for PUL2.0 and paired t-tests for other endpoints were used to assess differences at baseline and for deltas over time. Twenty-two patients were assessed at baseline, median age 9.2y, range 6.0 – 17.0 and ten for the 12-month follow-up visit, with fifteen expected to do so by October 2025. At baseline, only PUL2.0 total score and handgrip were higher in the dominant arm compared to non-dominant (36.5 vs 35.0, p=0.003 and 8.0 vs 7.2Kg, p=0.033). No significant dominant – non-dominant difference for delta over time was seen for any of the endpoints, including PUL2.0 total score, –2.0 (4.3) vs. –1.0 (3.3), shoulder abduction, –7.6 (14.3) vs. –6.5N (20.6), elbow isometric flexion, – 1.9 (6.1) vs. – 3.9N (10.9) and handgrip –0.2 (1.8) vs. –0.4Kg (2.0). Ongoing analyses include quantitative MRI results. Our results strengthen clinical observations that differences in DMD progression between dominant and non-dominant upper limbs are limited. This paves the way for clinical trials using unilateral and/or local IM interventions with a patient as his own control design.