Massimo Venturini MD, Presenter: Nothing to Disclose

Giulio Cossu, Abstract Co-Author: Nothing to Disclose

Letterio Salvatore Politi MD, Abstract Co-Author: Nothing to Disclose

Michele Colombo, Abstract Co-Author: Nothing to Disclose

Giulia Agostini, Abstract Co-Author: Nothing to Disclose

Alessandro Del Maschio MD, Abstract Co-Author: Nothing to Disclose

DMD, a syndrome characterized by progressive absence of dystrophin protein, causes progressive muscle degeneration, paralysis and death. Corticosteroids are not effective, while novel therapies (gene/stem cells) are on work. Our aim was to assess MABs intra-arterial infusion in 5 dystrophic children, at escalating dose, to preliminarily assess the safety.

After the approval of our institutional ethical committee and obtaining written informed consent from the children’s parents, every 2 months 5 DMD children (5 males, mean age=10 years) at a different disease stage under immunosuppressive treatment (tacrolimus) were submitted to 4 HLA-identical allogeneic MABs intra-arterial infusions each (2 in lower limbs, 2 in lower and upper limbs) at escalating dose. Intra-arterial infusions were performed at the level of the common femoral arteries (lower limbs) and the axillary arteries (upper limbs) using a transfemoral approach (4-Fr catheter): arteriography was performed before and after MABs infusion. Efficacy was assessed every 2 months by quantitative strength measurements (Kin-Com-test), thighs/legs fibro-fatty degeneration/quantification (MRI), and after 8 months by gastrocnemius biopsies (dystrophin restoration).

The 20 intra-arterial MABs infusions were regularly performed with no peri-procedural complications, except for a case of iliac vasospasm successfully treated. The only relevant complication was 1 focal thalamic ischemia of 1-cm (MRI) that occurred 5 hours after the fourth infusion in one child, after sporadic atrial fibrillation (ECG) (Atrial-fibrillation-related-thrombosis? Late vasospasm?), without clinical consequences. Relative stabilization/decrease in disease progression was observed in all the children. At MRI, a stabilization of fibro-fatty degeneration was more evident in a child treated at an earlier disease stage, the only that demonstrated a significant dystrophin restoration at Gastrocnemius biopsy.

Our preliminary phase 1 study on MABs intra-arterial transplantation in DMD children was relative safe, partially effective with encouraging perspectives. A larger cohort of children and a longer follow up are needed.

A higher MABs intra-arterial concentration, transplanted exclusively in the lower limbs, at an early disease stage, could determine an increase of dystrophin restoration and a consequent improvement of the clinical outcome.

Venturini, M, Cossu, G, Politi, L, Colombo, M, Agostini, G, Del Maschio, A, First Phase-1 Study in the Treatment of Duchenne Muscular Dystrophy (DMD) by Multiple Intra-Arterial Transplantations of Mesoangioblasts (MABs) in 5 Dystrophic Children: Safety, Preliminary Efficacy, and Future Perspectives.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14017690.html