A study co-authored by UK DRI researchers has today (10 July) outlined a new cell-based system for studying Alzheimer’s disease, which could accelerate drug testing. The technology was also used to identify that the gene BACE2 may be involved in suppressing the progression of Alzheimer’s disease, opening avenues for new therapeutics.
A major challenge in testing Alzheimer’s drugs in clinical trials is that participants need to have symptoms. However, at this stage of disease progression, it is usually too late for treatments to have a significant effect, as many neurons have already died. The only current way to test potential preventative treatments is by identifying participants who are at higher risk of developing Alzheimer’s and seeing if treatments prevent the onset of their disease. This includes people with Down syndrome who have around a 70% chance of developing Alzheimer’s during their lifetime. This is because the extra chromosome 21 they carry includes the gene for amyloid precursor protein which causes early Alzheimer’s when at high levels or mutated.
In this new study led by researchers at Queen Mary University London and published in the Nature group journal Molecular Psychiatry, researchers collected hair cells from people with Down syndrome and reprogrammed them to become stem cells, which were then directed to turn into brain cells in a dish. In these brain-like cells or ‘cerebral organoids’, the researchers saw Alzheimer’s-like pathology develop rapidly, including the hallmark trio signs of Alzheimer’s disease - amyloid plaque-like lesions, progressive neuronal death and abnormal accumulations of a protein called tau inside neurons.
Lead researcher Professor Dean Nizetic from Queen Mary University of London, said: “This work represents a remarkable achievement, as this is the first cell-based system that has the full trio of Alzheimer’s-pathologies, without any artificial gene overexpression.
This system opens up the prospect for screening for new drugs aimed at delaying or even preventing Alzheimer’s before neuronal death starts.”
The researchers showed that the system could be used as a testing platform for drugs intended for early prevention. Taking two different drugs which are known to inhibit amyloid-beta production, the researchers showed that in just six weeks they had prevented the onset of Alzheimer’s-pathology. Although these two particular drugs have failed clinical trials for other reasons and therefore aren’t suitable treatments for Alzheimer’s, the team proved that the system can be used on any drug compound with quick results.
