EPSRC Project
A common feature of all dementias e.g. Alzheimer's, Parkinson's and Huntington's diseases are the presence of specific proteins in the brain, which due to having abnormal structures, accumulate into increasingly large assemblies and fibrils. These structures, which are present in many regions of the brain, are considered to be toxic and damage brain cells, leading to the symptoms of dementia. Using PET, we can now visualize the presence and distribution of some of these toxic proteins. However, with the present range of these chemical probes we can only image the late stages of these assemblies when most of the brain damage has occurred and so too late for effective drugs therapies. Therefore our aim is to develop next generation chemical probes that can image the earlier stages and structures of these abnormal proteins when they are considered most toxic and hence cause the most damage to brains cells. This would then create a powerful means for earlier more accurate diagnosis of dementia and a means of evaluating the new types of drugs that are been developed that target these assemblies. We have already synthesised a luminescent conjugated oligothiophene (pTP-TFE) which is considered to bind to earlier stages and smaller assemblies of these misfolded proteins. We are in the process of developing a new series of new chemical probes, and will apply chemical screening methods, medicinal chemistry, radiochemistry and biological assessments. The chemical probes with appropriate properties arising from this project we would then take forward with additional funding for human imaging studies. This collaboration is between Prof. Aigbirhio and Prof. Maria Spillantini (Department of Clinical Neurosciences), Prof. Christopher Hunter and Prof.David Klenerman (Department of Chemistry).