Gene Therapy Projects
Two new gene therapy projects pair experienced basic scientists who have deep knowledge of the Rett mouse models with elite researchers in the world of gene therapy.In both projects, healthy versions of the MECP2 gene will be delivered via a vector (similar to a Trojan horse) to the Rett mice.
Crystal/Bird Collaboration
Ronald C. Crystal, M.D., Adrian Bird, Ph.D.,
Weill Cornell Medical College, University of Edinburgh
This project will take place in the laboratory of Ron Crystal. Ron is one of only a handful of pioneering researchers around the world, who have brought gene therapy from the lab into clinical trials in humans. He is currently leading a gene therapy trial for Batten Disease, a fatal childhood neurological disorder.
Complimenting the Crystal expertise at gene therapy and clinical trials, is Adrian Bird of the University of Edinburgh. Professor Bird discovered MeCP2 protein in the early 1990's, developed several animal disease models and published the seminal reversal experiments in 2007.
In this project, the vector used will be the new generation AAVrh10 which has shown remarkable gene expression throughout the central nervous system. The hope is that the AAVrh10 vector will spread throughout the brain and ameliorate Rett symptoms.
Total RSRT UK funding to date: £57,360
RSRT UK funding delivered to this project in 2010: £22,600
RSRT UK funding delivered to this project in March 2011: £6250
RSRT UK funding delivered to this project in June 2011 £12,510
RSRT UK funding delivered to this project in September 2011: £16,000
Kaspar/Mandel Collaboration
Brian Kaspar, Ph.D., Gail Mandel, Ph.D.
Ohio State University, Oregon Health Science University
This team pairs the expertise of another leading gene therapist, Brian Kaspar, with another prominent Rett researcher, Gail Mandel. This collaboration will determine the clinical potential of scAAV9 in gene replacement strategies for Rett Syndrome. The Kaspar lab have already been successful in initial trials of SMN gene delivery with scAAV9 for treating a mouse model of Spinal Muscular Atrophy (SMA), completely rescuing the lethal phenotype seen in that disease model. The genetics of the Rett model are ideally suited to investigation of the clinical potential of scAAV9.
RSRT UK funding delivered to this project in 2010: £6400
RSRT UK funding delivered to this project in 2011 to date: £6250
Total RSRT UK funding to date: £12,650
It is crucial at this early stage to explore different vector delivery systems in parallel. The Crystal lab works with AAV10, a new generation vector with an increased distribution profile in the brain. The Kaspar/Mandel team will utilize the AAV9 vector, which can be delivered to the central nervous system via injections into the bloodstream rather than invasive injections into the brain.
Monica Coenraads, Executive Director of RSRT, Trustee of RSRT UK and parent of a child with the disorder comments, “While gene therapy intuitively makes sense for a single gene disorder there are inherent challenges - some related to the field of gene therapy and others unique to Rett Syndrome. When the risks and potential rewards are this high there is one crucial criterion: Alignment with the best people in the field. If anyone can get to the clinic with a gene therapy approach for Rett Syndrome, it’s the teams that we are funding.