Clinical Research Directory

Effect and Safety MABs Administration m.3243A>G Mutation Carriers

Sponsor: Maastricht University

Summary

The first primary objective is to assess the effect of three intra-arterial administrations of autologous mesoangioblasts (MABs) with respect to improving muscle strength and reduce fatigue of the treated biceps brachii (BB) compared to the untreated BB. The second primary objective is safety of three intra-arterial administrations of autologous MABs, which the investigators will assess by monitoring (serious) adverse events ((S)AEs), blood flow in left arm pre- and post-intervention, and neurological vital signs during 8h post-intervention observation in the hospital. Secondary objectives are to assess changes in muscle mass of the treated and untreated BB muscle, and microscopic changes and m.3243A\>G mutation load at tissue level in treated biceps brachii (BB) muscle at baseline and after treatment. Up to 20 adult m.3243A\>G patients will undergo a \~30mg m. biceps brachii muscle biopsy at visit 1. The first six eligible patients will enroll the clinical study based on their m.3243A\>G mutation load in skeletal muscle (50-90%) and mesoangioblasts (\<10%), and on a decreased BB muscle strength and increased fatigue. These 6 selected patients will visit the Maastricht University Medical Center for 8 additional times. From each patient, during visit 2 till 9: * BB muscle biopsies of the left arm will be collected (1x \~130 mg at visit 2 and 1x \~30mg at visit 9) * MRI of the BB muscles in both arms will be performed (visit 2 and 9). * Autologous MABs will be injected into the left arm via axillary artery delivery. Angiography will be performed before and after infusion to assess vascular obstructions, and the participant will be monitored in the hospital for 8 hours (visit 4,6,8). * Tc99m macroaggregated albumin (MAA) is infused to quantify blood flow to the BB muscle (visit 4). * A bout of maximal eccentric exercise of BB muscles on both sides will be executed at visit 3, 5 and 7. * BB muscle strength will be assessed using a Biodex dynamometer (visit 3-9) * venous blood samples will be taken for assessing muscle damage and inflammation markers (visit 3-9), kidney functioning, coagulation and viral screening (visit 1 and 2).

Official title: Assess Effect and Safety of Intra-arterial Autologous Mesoangioblast Administration to the Upper Arm of m.3243A>G Mutation Carriers

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