Lead Investigator: Professor Frank Gunn-Moore
Institution: University of St Andrews
Grant type: Project grant
Duration: 24 months
Start Date: June 2013
End Date: April 2016
Scientific Title: Novel drugs for treating Alzheimer's disease
What was the project, and what did the researchers do?
Alzheimer's disease is very complex, and it is thought that a single drug aimed at treating it will be unlikely to work. Some researchers are instead investigating the idea that a combination of drugs will be needed that will address several aspects of the condition. This includes targeting the toxic clumps of amyloid and tau protein that characterise the disease, preventing brain cells from dying and targeting other potential molecular causes or contributing factors of the condition.
This project focused on the last of these, and specifically on protecting a protein important in energy production called amyloid-binding alcohol dehydrogenase (ABAD). Amyloid binds to ABAD causing damaging changes to the brain's memory capabilities
The aim of this project is to start a programme to identify and develop drugs that specifically block this binding, and thus reducing disease.
What were the key results and how will this benefit people with dementia?
The researchers identified three unique sets of compounds that bind to ABAD and change its activity. They have then started to improve the chemical structures of these compounds and make them into more "drug-like" molecules. The next stage is to establish if these molecules can alter ABAD in living cells.
Additionally, they have also developed assays that can be used as screening tools for these compounds and we are applying them in a larger scale pharmaceutical setting with an industrial partner.
What happened next? Future work and additional grants
A recent grant awarded by Alzheimer's Society will allow postdoctoral researcher Dr Laura Aitken to continue this project and assess our drug like molecules at the cellular level. Another recent grant award from The Rosetrees Trust will also provide extra funding for consumables for this project.
How were people told about the results? Conferences and publications
Aitken L et al. (2016) Morphology-specific inhibition of β-amyloid aggregates by 17β-hydroxysteroid dehydrogenase type 10. ChemBioChem. 17: 1029-1037. DOI: 10.1002/cbic.201600081
Hroch L (2016) Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17β-HSD10 modulators for Alzheimer's disease treatment. Bioorg Med Chem Lett. 26(15):3675-8. doi:10.1016/j.bmcl.2016.05.087
Patents have been filed in the Czech Republic to cover some of the more promising compounds and any analogues that may be produced.
This work was presented at four conferences.