Basic science and preclinical development of cell transplantation for basal ganglia disorders

This programme provides the infrastructure, models and expertise to deliver human neurons (primary fetal, expanded fetal and stem cells) for use in clinical trials of cell transplantation in neurodegenerative disease. Specifically, in the Cardiff Brain Repair Group, we have established an ethically sourced supply and quality-controlled production of human embryonic brain cells for transplantation in both Huntington?s and Parkinson?s disease. We have also established the cell culture and animal model test systems to determine the precise preparation and implantation protocols that are most likely to lead to functional benefit (i.e. recovery in both motor and cognitive symptoms) in trials set to commence/resume in both PD and HD in 2011-12. Moreover, the UK is a world leader in fundamental stem cell biology which are likely to yield the next generation of pluripotential cells for therapy in a wide range of diseases; however, if we are to reap the benefit from the signficant government support and public investment in this area, we need to have in place the infrastructure to test the functional efficacy of new stem cell-based preparations, to prepare cells to clinical-grade quality standards, and to undertake clinical trials with skilled surgery and fully validated assessment protocols in well characterised patients. Thus, alongside the present establishment of proof-of concept with primary fetal cells, this programme grant underpins the expertise and infrastructure within the Cardiff Brain Repair Group that is required to take new stem cell therapies rapidly into clinical trial as soon as they become available. Without such proactive preparation and support, the UKs intellectual lead in fundamental stem cell biology is likely to be squandered to implementation and commercialisation elsewhere.

The UK is taking an international lead in developing stem cells for cell-based therapy applicable to a broad range of diseases. The purpose of this programme application is to address the translational gap to deliver clinical-grade human neuronal cells from primary, expanded and pluripotent origins for transplantation in clinical trials of human neurodegenerative disease. We complement other stem cell programmes in establishing and maintaining the infrastructure for ethically-sourced, safe, quality-assured processing of cells of clinical grade under regulatory licence, alongside establishing relevant patient cohorts, assessment programmes and clinical trial expertise, without which advances in basic cell biology cannot progress to human use or clinical trial. A major component of this programme is to develop and refine the animal models to evaluate alternative sources of cells with predictive validity of likely functional efficacy in man. Immediate applications are set to commence using primary fetal cells in 2011-2012 in Huntingtons disease and Parkinsons disease, with subsequent applications in stoke, and using expanded fetal progenitors, pending the availability of clinical grade stem cells.