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.
What it is
The concept behind gene replacement is simple. Deliver healthy genes to compensate for mutated genes. Gene replacement is a one-and-done strategy.
Why it matters
We know that the many symptoms of Rett are caused by mutations in a single gene, MECP2, which in turn makes a mutated protein. Numerous experiments in mice have shown that restoring levels of the MECP2 protein reverses symptoms. While we don’t yet know how the animal results will translate to people there is the expectation that dramatic improvements are possible.
Research directly funded by RSRT has resulted in two gene replacement industry programs, AveXis/Novartis and Taysha Gene Therapies, and two academic programs, University of Pennsylvania.and University of Edinburgh.
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.
Improvement seen in Rett mouse models treated with gene replacement is much greater than that of any drug tested to date.
A cure for Rett.
You want it.
We want it.
Great achievements happen when people stand up and say I’m in. I will be part of the solution!
Rett may be a rare disorder but together we are powerful.