gene therapy

$5,463,184 AWARDED

Gene Therapy Consortium 2.0

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.

The Beginning

RSRT first started funding gene therapy efforts in 2010 with a collaboration between Gail Mandel, PhD and Brian Kaspar, PhD. That collaboration led to our original Gene Therapy Consortium that launched in 2014 with the inclusion of Steve Gray, PhD and Stuart Cobb, PhD.

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 to date and suggests that significant benefit may be achieved in people. Based on that data AveXis committed to advancing a gene therapy candidate into clinical trials, and is on track to launch the first trial early in 2019.


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

While we fervently hope that the AveXis trial delivers significant and dramatic results we suspect there will be room for improvement. Fortunately, 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.


World-Class Team Takes on Next Gen Gene Therapy

In late 2018 RSRT announced a  Gene Therapy Consortium 2.0 comprised of a world-class team. The goal will be to have a next generation gene therapy product…should we need it.. ready for clinical testing by 2021. 


Meet the Consortium Members




James Wilson, MD, PhD, is a pioneer and a leader in the gene therapy field for decades and has played a pivotal role in the renaissance that the field is currently experiencing. He made a number of seminal discoveries including the discovery and development of the adeno-associated virus (AAV) that will be used by AveXis in the upcoming clinical trial. One of Dr. Wilson’s overarching objectives is improving delivery of genes to the brain which is of course extremely relevant to Rett Syndrome. Dr. Wilson is at UPENN where he runs the largest worldwide academic gene therapy program.

Adrian Bird is world’s leading expert on MECP2 and has become synonymous with Rett research. He discovered the MeCP2 protein in the early 1990s; made a mouse model that is used in hundreds of labs around the world; published the landmark paper that established the principle of reversibility for the disorder; and has made many significant contributions to the understanding of the function of the MeCP2 protein. Adrian Bird is a founding trustee of RSRT.

Dr. Cobb is an original Consortium member. His introduction to Rett came well over 10 years ago when he was approached by Professor Bird to conduct some neurophysiology experiments. He was a co-author on the 2007 reversibility paper and published the first gene therapy study in male mice using AAV2 and AAV9 vectors. Besides traditional gene therapy strategies Dr. Cobb is also pursuing RNA modification approaches.

The goals of the Consortium include:
• More deeply understand the function of MECP2 to develop more effective gene therapy products
• Design novel gene therapy cassettes to enable better regulatory control of the MeCP2 protein
• Design tunable systems that allow gene therapy to be turned off if necessary

Current Projects

Learn About our Roadmap to a Cure