Preclinical experience and perspectives of a clinical trial using CD133 stem cells

Introduction: cell therapy is one promising approach to correct genetic diseases by contributing to tissue regeneration; stem cells can be isolated from a healthy donor or, when possible from the same patient. In the first case cells will be transplanted under a regime of immune suppression while in the second case, cells will have to be genetically corrected before transplantation in the same patient. Methods: We isolated CD133+ cells from muscle biopsies of GRMD dogs. Dogs one year old, were treated with their own trasnduced U7exon 6-8 CD133+ cells. Dogs received 2 arterial systemic injections through a catheter that was introduced in the left femoralis artery and reached the aortic arch at the level of the left subclavia. Results: After the injection, all treated dogs had a clinical performance improvement. All animals were analysed at different times; most of the biopsies in all muscles had a morphological amelioration when compared to untreated dogs. Dystrophin expression in the biopsies was variable, ranging from 2 to ≥ 7% in several biopsies of the injected legs. Western blot analysis of different biopsies of the same muscles confirmed the presence of different amount of dystrophin, varying from an undetectable signal to around 6%. Discussion/Conclusion: Because of these results, we plan a pilot clinical trial, based on intra-muscular and intra-arterial transplantation of autologous engineered muscle derived CD133+ cells. Efficacy and possible adverse effects will be evaluated to test whether this approach may represent a first step towards an efficacious therapy for muscular dystrophy