Maastricht University is recruiting patients for a Phase I clinical trial with autologous muscle stem cells in m.3243A>G mutation carriers (MELAS, MIDD syndrome). Please contact Dr. René De Coo if you have patients that are eligible.
Rationale:
Mitochondrial disorders are progressive, often fatal multisystem disorders, in 20-25% of the cases caused by heteroplasmic mutations in the mitochondrial DNA (mtDNA). At this moment, there is no effective treatment known to influence the disease process or manifestation. Myogenic stem cell-based therapies complementing defective muscle cells and fibres, are highly promising to combat the myopathy and exercise intolerance which affect >50% of heteroplasmic mtDNA mutation carriers. Myogenic stem cells called mesoangioblasts (MABs), are currently the only myogenic precursors that fulfil all criteria to be used as advanced therapy medicinal product (ATMP) for systemic treatment. The researchers have demonstrated that MABs of most m.3243A>G carriers contain no or only a low amount (<10%) of the mtDNA mutation, allowing direct ex vivo expansion of patient-derived MABs. The overall aim is to induce muscle regeneration using these autologous MABs with a mutation load of <10%, as an advanced therapy medicinal product (ATMP).
Objective:
The phase I/IIa trial will consist of an intra-arterial injection (via catheter in femoral
artery) of the autologous MABs in the left lower leg of 5 m.3243A>G patients. The primary
objective is assessing safety of administration of autologous MABs, which have not been used as treatment before in humans. Secondary objectives are (1) to assess homing of the labelled
autologous MABs to the tibialis anterior muscle 24 hours after i.a. delivery, and (2) assess
effectiveness at the tissue level by measuring myogenesis and mtDNA mutation load of
treated tibialis anterior muscle compared with untreated muscle from the contralateral leg.
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following
criteria:
- Written informed consent
- Age: 18+
- Sex: male/female
- Patients with the m.3243A>G mutation
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from
participation in this study:
- Use of anti-coagulants, anti-thrombotics and other medication influencing coagulation
- Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
- Current history of drug abuse
- Deficient immune system or autoimmune disease
- Significant concurrent illness
- Ongoing participation in other clinical trials
- Major surgery within 4 weeks of the visit
- Vaccination within 4 weeks of the visit
- Pregnant or lactating women
- Psychiatric or other disorders likely to impact on informed consent
- Patients unable and/or unwilling to comply with treatment and study instructions
- Any other factor that in the opinion of the investigator excludes the patient from the study
- A history of strokes
- Allergy for contrast fluid
- Peripheral signs of ischemia or vasculopathy
