Alzheimer's Society drug discovery fellow Caroline Woffindale
Care and cure magazine - Winter 2015
Alzheimer's Society drug discovery fellow Caroline Woffindale is in the first year of a three-year funded project in the Translational Neuroscience and Dementia Research Group led by Professor Simon Lovestone at the University of Oxford.
As a student, I became increasingly interested in how the brain is able to store and retrieve the complex information of our memories. As I learned more about the devastating consequences that occur when anything goes wrong with these processes, such as dementia, I decided that I wanted to do all that I could to help. With the number of people with dementia predicted to grow, and unfortunately having now witnessed relatives begin to go through this experience, my desire to understand the causes of Alzheimer's disease and to help to find a cure for this distressing condition has grown even stronger.
Two key proteins, amyloid and tau, have been shown to be important in the development of Alzheimer's disease. However, we still don't know if or how these two proteins may interact to cause the damage to brain cells responsible for Alzheimer's disease. Work within our lab previously revealed a potential link between the toxic effects of both amyloid and tau via another protein called DKK1.
This work, supported by Alzheimer's Society funding, showed that the lab-based treatment of brain cells with either amyloid or DKK1 proteins led to the activation of several genes, which appeared to reduce the toxic effects of amyloid and tau proteins. By providing a potential link between two established proteins associated with Alzheimer's disease, these genes may represent new targets for drugs.
My fellowship is focusing on identifying drugs that target this specific pattern of gene activation and might therefore be useful in the treatment of Alzheimer’s disease. To do this, I am using an online resource called the Connectivity Map, which can be used to link genes, drugs and diseases. The Connectivity Map is a database of gene activation data collected from human cells that have been treated with a large number of different drugs. Using the genes identified by our previous work, it allows us to identify existing drugs that may be able to reverse the pattern of gene activation seen in Alzheimer's disease.
Using this approach, I have identified a number of drugs, many of which are already approved for the treatment of other diseases, which appear to influence our genes of interest. I am now testing these potential drugs in rat brain cells which mimic Alzheimer's disease to determine whether or not they are able to have an effect on the disease.
We are very grateful to Alzheimer's Society for all its support, which allows our work to continue. It is an exciting time to be involved in Alzheimer's disease research, with the next big breakthrough hopefully just around the corner!