Duchenne muscular dystrophy (DMD) is a lethal X-linked disease, caused by mutations of the dystrophin gene leading to muscle degeneration and wasting. EMG is an objective electrophysiological biomarker of muscle fiber function and has been used extensively to study muscular dystrophies. A novel DT-DEC01 therapy of Dystrophin Expressing Chimeric (DEC) cells was created by fusion of human myoblasts derived from normal (allogeneic) and DMD-affected (autologous) donors.
This study aimed to determine the preliminary efficacy of DT-DEC01 therapy by needle electromyography (EMG).
Primary endpoint was EMG assessment of motor unit potential (MUP) duration (most reliable parameter, independent of the distance between the needle and the firing unit) in selected muscles following intraosseous administration of a single dose of DT-DEC01 therapy (2×10^6 cells / kg) in 5-18 years old boys (n = 3) with genetically confirmed DMD (Bioethics Committee approval no.185/2022). No immunosuppression was used.
Secondary endpoints: MUP amplitude and polyphasic MUP percentage. EMG assessment was presented as the percentage of the initial value (mean MUP duration/mean MUP amplitude)
Results: Average follow up was 9.6 months (range 8-12). No therapy related AE or SAE were reported.
Patient #1 ambulatory (7-year-old, deletion Exon 3-12) :12-months post DT-DEC01, EMG revealed increased MUP duration in: biceps (+91%/+96%); deltoideus: (+28%/+82%), gastrocnemius (+30%/+115%), rectus femoris (+40%/+57%).
Patient #2 non-ambulatory: (15-year-old, deletion Exon 48-50): 9-month post DT-DEC01 EMG revealed increased MUP duration in: biceps (+140%/+286%); deltoideus (+65%/+81%), gastrocnemius (+30%/101%), and maintained in rectus femoris.
Patient #3 ambulatory: (6-year-old, nonsense mutation): 8 -months post DT-DEC 01 EMG revealed increased MUP duration in: biceps (+6%/+59%), gastrocnemius (+5%/-29%) rectus femoris (+29%/+108%).
This study confirmed improvement of MUP duration on EMG and increase in MUP amplitude in most examined muscles of both ambulatory and non-ambulatory patients. Percentage of polyphasic MUP increased in assessed muscles up to 12 months after intraosseous DT-DEC01 administration. We hypothesize this to be an electrophysiological sign of a muscle response to treatment by regrowing and remodeling the shape and volume, giving rise to polyphasic MUP.