Cell-mediated skipping of exon 51 for the genetic correction of dystrophin, based upon a single injection of autologous mesoangioblasts (MABs) in individual skeletal muscles of five non-ambulant patients affected by Duchenne Muscular Dystrophy: a non randomized, open-label, phase I/IIa study

Prior treatment

• Ongoing participation in any other therapeutic clinical trial or treatment with exon skipping oligonucleotides. Use of steroids is considered standard care and therefore permitted.
• Change of medication related to DMD within last 3 months with the exception of adjustment based on weight gain of current medications.

Other illness

• Positive hepatitis B surface antigen, hepatitis C antibody test, or Human immunodeficiency virus (HIV) test, TPHA test.
• Presence of significant impairment of renal or hepatic function.
• Presence of immune deficiency, neoplastic or autoimmune disease (based on clinical history).
• Bleeding disorder.
• Any known allergies to products likely to be used in the study.

Lab values

• Prior or ongoing medical condition (e.g. concomitant illness, psychiatric condition, behavioural disorder, drug abuse), medical history, physical findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.
• LVEF (Left Ventricle Ejection Fraction) < 45% of a healthy subject or ECG finding significant for underlying cardiac impairment.

Other

• Presence of severe scoliosis (curve >50°).
• Pulmonary function tests assessed by spirometry (if cooperative) of FEV1 and FVC <30% of the predicted values. If unable, pulse oximetry < 95 % in room air.

• Age between >= 12 and <18 years at time of study entry, provided that participants matching the eligibility criteria can be identified.
• Non-ambulant at the time of recruitment.
• Confirmed diagnosis of DMD with documented exon 51 skippable mutations in dystrophin gene.
• Progression of muscle degeneration =< to 50% reduction of muscle mass as determined by quantitative MRI (grade 2: Kinali et al. 2011).
• Written informed consent of caregivers of DMD patients and patient’s assent.