Neuroprotection in Parkinson's Disease
Professor David Dexter
Professor Dexter has been principally involved in research relating to Parkinson’s Disease and neurodegeneration for over 27 years. This research theme has stemmed and developed from my PhD studies. Since that time I have developed a consistent theme of research investigating the mechanisms underlying neurodegeneration in Parkinson’s disease and subsequently developing novel therapeutic approaches to prevent neurodegeneration or modify the disease symptoms. The research has yielded some seminal papers particularly in the field of oxidative stress and mitochondrial dysfunction. Current research has mainly developed from these ideas and is underpinned by an extensive grant portfolio and is carried out by a research team of 15 staff.
Current research topics include:
- The development of antioxidants and metal chelators as neuroprotectory agents for treating Parkinson’s.
- Role of glutamate metabotropic receptor drugs in symptom amelioration and neuroprotection in Parkinson’s.
- Role of inflammation in the disease process and the beneficial effects of anti-inflammatory agents.
- Sex differences in the incidence of Parkinson’s disease and the neuroprotectory effects of estrogen.
- The involvement of stress in the development of Parkinson’s.
- Role of genetics, risk genes and Gene expression studies in Parkinson’s.
- Role of histone deacetylases (HDAC) in the neurodegenerative process in Parkinson’s and the potential use of HDAC-inhibitors.
- Development of nano-particles as drug delivery vehicles across the blood brain barrier
- Involvement of Calcium homeostasis in the neurodegenerative process in Parkinson’s
- Developing animal and cellular model of Parkinson’s.
- Running and developing the Parkinson’s UK Tissue Bank
Dr Dexter was the principle person responsible for establishing the Parkinson’s UK Tissue Bank in 2002 via a program grant from the Parkinson’s UK with the tremendous assistance of Professor R Reynolds, scientific director MS Tissue Bank. The Tissue Bank is now jointly funded together with its sister Multiple Sclerosis Tissue Bank, by a programme grant from the MS Society and Parkinson’s UK. The joint Tissue Bank now has a growing list of almost 10,000 potential donors, has collected over a 1,000 brains and supplies researchers with high quality tissue both in the UK and around the world. The joint Tissue Bank is recognised as one of the leading international resource centres for providing high quality, highly characterised samples of Parkinson’s and MS brain, spinal cord and CSF. Dr Dexter has collaborated in the international Parkinson’s disease consortium to supply Parkinson’s brain samples for multinational GWAS studies which has recently discovered 15 risk genes for the development of Parkinson’s disease which has been published in the Lancet.
Both Tissue Banks were involved in a Frame Work 6 EU Network of Excellence grant – Brain Net II –where 18 Tissue Bank across Europe to standardise procedures and quality, improve tissue supply for research and advance research into common neurodegenerative conditions. In addition, Dr Dexter has participated in and helped develop EU COST actions in chemistry for biological applications for the past 20 years. These have allowed extensive collaborations across Europe with synthetic chemists, physical chemists and biochemists for the development of novel compounds and models.
The principal focus of the research group has been to understand the neurodegenerative mechanisms causing Parkinson’s disease utilising human tissue along with cellular and in vivo animal models and to identify drug target sites for the development of novel therapies. Such novel therapies are then tested on a variety of animal models of Parkinson’s with the long-term goal of translating successful pre-clinical therapeutics into clinical trials. A major recent achievement in this translational approach has been the initiation of a pilot clinical trial in Parkinson’s disease with the iron chelator Deferiprone. We were the first group in the world to conclusively prove that increased brain iron levels are associated with the neurodegenerative process in Parkinson’s and subsequently went on to demonstrate that iron chelators can remove excess brain iron and are neuroprotective in animal models of Parkinson’s which has given support for the clinical trial. With the support of the Parkinson’s disease clinical trials unit at Imperial, hopefully this pipeline approach will yield further clinical trials to hopefully halt this devastating disease.
Dr Dexter also has a cross faculty collaboration with Dr Alex Porter, in engineering, working on the development of nano-particles as drug delivery platforms for not only delivering drugs across the blood brain barrier but also then to target specific cell types in the brain.
Direct Funding of Research to Fight Parkinson's: Imperial College is a registered charity and we welcome direct donations to fully fund or part fund research into this highly delbilitating disease. No donation is too small since together we can cure Parkinson's.