Gene Therapy Consortium

Stuart Cobb, University of Glasgow | Steven Gray, UNC | Brian Kaspar, Nationwide Children’s Hospital | Gail Mandel, Oregon Health & Sciences University

$3,053,620 AWARDED

We know from Adrian Bird’s 2007 experiments that Rett symptoms in mice are reversible when the expression of the MeCP2 protein is brought back to normal. But a huge question remains—how do we go from recovering mice to recovering children? Gene therapy may be one answer to that question. In 2013 the RSRT-funded labs of Gail Mandel and Adrian Bird showed, for the first time, the reversal of multiple symptoms in adult female mice using gene therapy.

In 2014 RSRT launched the MECP2 Gene Therapy Consortium, a bold international collaboration between four laboratories who together bring all the necessary skills to determine if gene therapy is a feasible approach and if so to get us to clinical trials as quickly as possible

While traditional drug approaches will likely be restricted to correcting specific aspects of what goes wrong in Rett it is conceivable that gene therapy can correct the cause of Rett at its very source and thus provide a profound recovery of function.

Consortium members are working on the following:

  • Optimize dose, delivery route, and vector design to deliver replacement MECP2 gene.
    To date gene therapy has only been done in mouse models that have no Rett protein at all.
  • Individuals with Rett typically have some MeCP2 protein although it is mutated. The Consortium will conduct gene therapy in mouse models that have been designed to mimic actual human mutations to experiment with a more realistic scenario.

Girls with Rett Syndrome are “mosaic” for mutations. About half of their cells have normal functioning MECP2 and half the cells are mutated. The Consortium will design novel vectors that can preferentially target mutant cells while leaving normal cells alone.

Current Projects