gene therapy

$4,707,696 AWARDED

Gene Therapy Consortium

Rett Syndrome, as awful as the symptoms may be, provides us with several enormous advantages. First we know the cause: mutations in a single gene: MECP2. Second, Rett is not degenerative – brain cells don’t die. Third, work from RSRT trustee, Adrian Bird, suggests that the symptoms of Rett need not be permanent. These three facts make gene therapy an attractive therapeutic strategy.

Gene therapy is the lead program of our Roadmap to a Cure

In 2014 we launched a bold international collaboration of two gene therapy labs, Brian Kaspar and Steven Gray, and two MECP2 labs, Gail Mandel and Stuart Cobb. Together these labs brought together all the necessary skills and experience to determine if gene therapy is a viable therapeutic.

The Consortium worked through numerous challenges involving vector optimization (the Trojan horse that delivers the gene into a cell), gene construct optimization (what you package into the vector that regulates MeCP2 protein production), gene therapy dosage, and the best route to deliver it.

The data generated by the Consortium exceeded our expectations. They were able to develop a gene therapy product candidate with impressive efficacy, safety and delivery characteristics. Importantly, the magnitude of improvement in the mouse models of Rett is much greater than that of any drug tested and suggests that significant benefit may be achieved in people. We expect improvements, at least to some degree, regardless of age.

Based on the Consortium data the biotech company, AveXis, has now committed to advancing a gene therapy candidate into clinical trials.

Technological advances in gene therapy are happening quickly with more effective vectors being discovered that can carry larger DNA cargos and target a greater percentage of brain cells. While we anticipate encouraging results with our first clinical trial there will undoubtedly be room to improve. We have therefore recently awarded continued funding to the Gene Therapy Consortium to support second-generation gene therapy programs to leverage all technological advances.

Without RSRT championing gene therapy, we would not be where we are today. Bringing our expertise and focus on rare monogenic diseases, we are excited by the possibility that gene therapy may address the needs of individuals with Rett Syndrome.

Brian Kaspar

Chief Scientific Officer, AveXis

Meet the Consortium Members

The Consortium is comprised of a gene therapy lab, Steven Gray, and two labs with expertise in the Rett gene and mouse models, Gail Mandel and Stuart Cobb. In late 2016 we renewed funding and welcomed Alysson Muotri to the Consortium.


Steven Gray is at University of North Carolina, Chapel Hill, where he has successfully navigated a gene therapy program from the bench into human clinical trials.


Stuart Cobb is at the University of Glasgow and was one of the authors of the reversal paper published in 2007. 


Gail Mandel, from OHSU, has been involved in Rett Syndrome research for over a decade and has made seminal discoveries.


Alysson Muotri has been working on Rett Syndrome for over a decade, first in the laboratory of his mentor, Fred (Rusty) Gage at the Salk Institute, and now at UCSD.


Dr. Wilson has been a pioneer and a leader in the gene therapy field for three decades. He runs the largest academic based gene therapy program in the world where he is currently focused on improving delivery of genes to the brain.

Beyond Traditional Gene Therapy

Targeting the root problem in Rett, MECP2, can be done either at the DNA level (gene therapy or MECP2 Reactivation), the mRNA level or protein level.

Both the DNA and protein approaches carry a risk of potential dosage problems (too much MeCP2 may be harmful). An alternative approach is to use a technology called Spliceosome-Mediated RNA Trans-Splicing (SMaRT). This technology allows a mutation to be spliced out and repaired in RNA. The advantage is that this approach avoids any potential over-expression issues. Consortium member, Stuart Cobb, is working on this approach.

Gail Mandel of the Consortium is working on yet another approach, RNA editing. The possibility of correcting mutations in RNA has profound therapeutic potential, but had remained largely theoretical. Our focused investments have already demonstrated the potential for correcting MECP2 mutations in RNA in cells. We are currently increasing our investment to improve the editing efficiency and to identify optimal delivery methods.

Current Projects

Learn About our Roadmap to a Cure