Journal
EMBO MOLECULAR MEDICINE
Volume 7, Issue 12, Pages 1513-1528Publisher
WILEY
DOI: 10.15252/emmm.201505636
Keywords
cell therapy; Duchenne; dystrophin; mesoangioblast; MRI
Categories
Funding
- EC FP7 IP Optistem [223098]
- Telethon Italy
- Duchenne Parent Project (Italy)
- CureDuchenne
- Italian Ministry of Health [RF-2009-1547384]
- MRC [MR/J006785/1] Funding Source: UKRI
- Medical Research Council [MR/J006785/1] Funding Source: researchfish
Ask authors/readers for more resources
Intra-arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first-in-human, exploratory, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor-derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2-month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor-derived dystrophin in 1. Intra-arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available