The Buzz Blog - Research News
Bee For Battens is pleased to announce that it has entered into a two year project with Dr Steven Gray of The Gene Therapy Centre of the University of North Carolina , one of the United States Leading Gene Therapy Lads.
The Project which was sanctioned on Jan 18th 2011, the 2nd Anniversary of Batten Disease sufferer Saoirse Heffernan, who died form the condition aged just 5. Saoirse's brother Liam, the only remaining child of parents Tony & Mary Heffernan also suffers from Late Infantile Batten Disease (CLN2). The childrens mother, Mary stated; "We hope that our charities investment into this trial will benefit other children affected by this condition around the world and leads to a cure for this cruel disease which will eventually take both of our precious children".
This new funding announcement provides hope for children affected by Batten Disease, a rare and fatal neurological disorder affecting children. Matching research funds were pledged by the Health Research Board of Ireland. Dr. Steven Gray will lead the project development at UNC in collaboration with Dr. Jude Samulski (Director, UNC GTC), Dr. Mark Sands (Washington University in St. Louis, USA), and Dr. Jonathan Cooper (King’s College, London, UK).
Gene therapy for Batten Disease, in particular for the early infantile (INCL, CLN1 mutation) and late infantile (LINCL, CLN2 mutation) forms, has shown considerable promise in laboratory studies. These approaches have utilized a viral-based gene delivery platform, based on the adeno-associated virus (AAV). AAV is the only human virus that isn’t associated with any human disease, and when delivered to the brain it can provide sustained long-term expression of the packaged gene, potentially providing a life-long therapeutic effect from a single administration. For these reasons, scientists have basically used AAV as a molecular delivery truck, to deliver therapeutic genes to humans in over 75 human clinical trials. Two of these clinical trials have been for LINCL, and while these trials have concluded the AAV itself is safe, they have not reported any therapeutic benefit thus far.
A major reason why the encouraging laboratory studies have not worked in humans could easily be a simple matter of scale. It would take many injections to target all brain areas in humans, and this involves cutting-edge and risky neurosurgery. Even if these injections are done under the best possible conditions, only small pockets of cells within the brain are treated, leaving large portions of the brain and the entire spinal cord untreated.
The UNC GTC specializes in developing new versions of AAV and newer delivery methods, focusing on creating gene delivery platforms that can be successfully applied to humans. As a consequence, the UNC GTC has supported 12 human clinical trials across the world, including the first ever gene therapy trial using AAV (which was for Canavan Disease). The UNC GTC has recently developed a gene delivery platform for achieving widespread distribution of the therapeutic gene across the entire brain and spinal cord. This platform has been validated in mice, pigs, and monkeys. This advancement utilizes a different type of AAV than has been used for Batten Disease before, and this AAV shell will distribute the therapeutic gene through the brain and spinal cord after being injected into the cerebrospinal fluid in the lower spinal cord. The procedure is very similar to a spinal tap. Some of the pilot funding for these studies was provided by Jasper Against Batten, another private foundation supporting Batten Disease research.
This proposal aims to test this global gene delivery platform in mice with Batten Disease, to see if it imparts a therapeutic benefit over previous gene therapy approaches, as expected. If these studies are successful, existing large animal biodistribution studies would pave a clear path forward for human translation, following appropriate toxicology studies. For human applications, the AAV-based intrathecal gene delivery platform would provide a minimally-invasive injection route, a moderate dose that could be readily manufactured at clinical grade by the UNC GTC, and efficient expression of the therapeutic gene throughout the entire brain and spinal cord volume that can be scaled to humans.
Bee For Battens is also pleased to welcome some additional support to its 2013-2015 research projects for 4 other parent founded organsiations based in the United States. The American organizations are Jasper Against Batten,Taylors Tale, Drew’s Hope, Hayden’s Batten Disease Foundation, Inc. and A Cure for Nick.
The collaborating organizations were founded by family and friends of children afflicted with Batten disease, which is one of approximately 7,000 rare diseases that afflict 30 million people in the United States, or one in 10 Americans, and an estimated 350 million people worldwide. The cost in terms of human suffering and huge financial burdens make finding rare disease treatments a top public health priority.