An American team has successfully tested the transfer of the ACVR1 gene, the transfer of an allele-specific silencing microRNA ACVR1R206H, and the combination of both.
- Gene therapy in human iPS cells of FOP abolishes activin A signalling and aberrant osteogenic and chondrogenic differentiation.
- Local treatment of traumatic heterotopic ossifications in adult mouse models of FOP or systemic newborn mice reduces traumatic endochondral formation, but not the inflammatory and fibroproliferative response.
- The combination of ACVR1 gene transfer and silencing of the mutated allele was most effective in suppressing both traumatic and spontaneous heterotopic ossifications.
- The doses of AAV9 required for systemic administration would be 4 to 10 times lower than those used in Zolgensma® and would increase the tolerability of future treatment.
Given the incomplete similarity of the pathology of the mouse model with the human disease and the unexplored effects of this gene therapy on non-skeletal cells, the authors conclude that the future initial use of the gene therapy in humans should be as a local treatment at the early stage of relapses or as a preventive treatment before surgery.
