This is RSRT’s lead strategy and the one closest to clinical trial.
Rett Syndrome, as awful as the symptoms may be, provides us with several big advantages. First, we know the cause: mutations in a single gene, MECP2. Second, Rett is not degenerative – brain cells don’t die. All the different kinds of brain cells are present and all are in the correct places. Third, work from RSRT trustee Adrian Bird suggests that the symptoms of Rett need not be permanent. These three facts make gene replacement an exciting and promising therapeutic strategy.
Early Leaps, Promising Result
RSRT started funding gene replacement efforts in 2010, at a time when gene therapy for neurological disorders was still considered science fiction. Encouraging data led to the launch of the RSRT-funded Gene Therapy Consortium in 2014. The Consortium included gene therapists Brian Kaspar and Steve Gray, and MECP2 experts, Stuart Cobb and Gail Mandel.
The Consortium worked through challenges involving vector optimization (the Trojan horse that delivers the gene into a cell), gene construct optimization (what you package into the vector), dosage, and the routes of administration into the body.
The data generated by the Consortium exceeded our expectations. They developed a gene replacement product candidate with impressive efficacy, safety, and delivery characteristics. The magnitude of improvement seen in Rett mouse models treated with gene replacement is much greater than that of any drug tested to date and suggests that significant benefit may be achieved in people.
Importantly the Gene Therapy Consortium incubated two industry programs and two academic programs.