A high-throughput small molecule screen to correct TDP-43 induced stathmin-2 cryptic splicing in ALS and FTD
Prof Adrian Isaacs (UK DRI at UCL)
Partnering with the Alzheimer’s Research UK’s (ARUK) Drug Discovery Alliance - UCL Drug Discovery Institute (ARUK DDI), Prof Isaacs’ team are performing a large-scale drug screening campaign of 176,000 compounds to identify small molecules that restore neuronal health in ALS/FTD.
“We’ve developed a highly robust assay and have now successfully screened 125,000 compounds. We have several hits to take forward which is very exciting! This would not have been possible without funding from the UK DRI translation scheme and crucially our very close collaboration with the DDI, which has transformed our ability to perform meaningful drug discovery. We look forward to working together on the next steps of the project.”
Identification of novel, brain-penetrant inhibitors of the C3bBb convertase for treatment of neurodegenerative diseases
Prof Paul Morgan (UK DRI at Cardiff)
In this project led by Prof Paul Morgan, complement biology experts from the UK DRI at Cardiff have joined with ARUK Drug Discovery Alliance - Oxford Drug Discovery Institute (ARUK DDI) to identify inhibitors of the alternative complement pathway that, crucially, penetrate into the central nervous system, and have the potential to target harmful neuroflammation associated with neurodegenerative disease.
“We’ve now developed the high-throughput screening methodology and the first compound screens are planned in the next month. I am confident that we will obtain hits from this screen that we can further evolve towards future drugs. Collaboration with Oxford DDI has been essential for this project – although we know the complement system very well and can develop unique assays, we neither have the capacity to run at scale nor access to relevant compound libraries. They help fill these gaps.”
Non-invasive brain stimulation intervention to ameliorate pathogenic sleep-arousal impairment in dementia
Dr Nir Grossman (UK DRI at Imperial)
In collaboration with Prof Derk-Jan Dijk and Dr Ines Violante (UK DRI Care Research and Technology, based at the University of Surrey), Dr Grossman and his team are working to develop a non-pharmacological intervention for sleep disturbances in dementia, based on a novel sensory stimulation that augments brain activity.
“The translational award has been helping us to further improve our interventional concept and expand the evidence of sleep features augmentation. The outcome will guide the next, larger scale investigation and strengthen our ability to fund it.
