A team supported by the AFM-Telethon has provided proof-of-concept for the efficacy of a dual gene therapy approach in a mouse model OPMD.
Oculopharyngeal muscular dystrophy (OPMD) is due to an abnormal increase in the number of repetitions of a GCG triplet in the PABPN1 gene that disrupts the functioning of the muscle cell. Usually, the number of GCG repeats of the PABPN1 gene is between 1 and 10 depending on the individual: in OPMD, this number varies between 11 and 18 repetitions. This results in an accumulation of abnormal PABPN1 protein in the nucleus of skeletal muscle cells, which results in the formation of aggregates.
In an article published in March 2017, an international collaboration involving researchers from the Institute of Myology’s Myology Research Center reported on the efficacy of a dual gene therapy approach that involved administering, via a vector, RNA interference (RNAi), which causes the destruction of the normal or abnormal PABPN1 protein, and using a second vector, the normal “optimised” PABPN1 gene, which enables the production of a PABPN1 protein that resists destruction by the RNAi.
The administration of this “dual gene therapy” to OPMD mice results in a considerable decrease in the amount of aggregates in the muscle cell nuclei, an improvement in muscle degeneration, a decrease in muscle fibrosis, and an increase in the muscle strength of mice. This therapeutic pathway has also been shown to be effective in the cells of OPMD patients.
This is the first study to demonstrate a proof-of-concept of the efficacy of dual gene therapy in an OPMD model mouse.
