CFH1b KIT - Repurposing of an approved drug for Frontotemporal Dementia

Project: Other projectOther internal award

Project Details

Layman's description

Frontotemporal Dementia (FTD) is an early onset dementia starting in the fourth/fifth decade of life and is closely related to motorneuron disease (MND). 50% of FTD cases (10% MND) have a genetic cause. As yet, there is no therapy or cure for FTD. We have developed a fruit-fly with genetic FTD-MND to model aspects of the disease. We have also developed a model of FTD-MND using rat neurons in culture. Using an identified Federal Drug Administration (FDA) approved drug normally used for a liver complaint we have rectified collapse and death of neurons we see in our FTD-MND models. The drug is currently out of patent and this study aims to repurpose this compound for FTD-MND. We have also potentially identified a receptor for the drug that will allow us to develop intellectual property for our discoveries to facilitate the development of better and more effective drugs with commercial interest.

Key findings

We have now purified the ligand binding domain of the nuclear hormone receptor we have identified as the potential UDCA receptor. A key characteristic of nuclear hormone receptors is that they are stabilised by binding of their ligand. We find that the hormone receptor is generally unstable during purification, but is stabilised very robustly by micro-molar levels of UDCA. We have submitted a project application to Alzheimer's Research UK, which was initially rejected but with a request for resubmission. Specific feedback was given. Resubmission will be 23/01/19
Effective start/end date2/04/1831/10/18