Researchers develop early prevention drug testing platform for Alzheimer’s disease

A study led by Queen Mary University in London discovered a gene that could naturally suppress the signs of Alzheimer’s disease in human brain cells. Scientists have also developed a new rapid drug screening system for treatments that can potentially delay or prevent disease.

A major challenge in testing Alzheimer’s disease drugs in clinical trials is that participants must have symptoms. However, because many brain cells are already dead, once a person becomes symptomatic, it is usually too late to have a significant effect on treatment.

The only current way to test potential prophylactic treatment is to identify participants at high risk of developing Alzheimer’s disease and to see if the treatment prevents the disease from developing. This includes people with Down’s syndrome (DS) who have about 70% chance of developing Alzheimer’s disease in their lifetime. This is because the extra chromosome they carry contains the gene for the amyloid precursor protein. Amyloid precursor protein causes early Alzheimer’s disease when overdosed or mutated.

In this study, Published in Molecular psychiatry, Researchers instructed to collect hair cells from people with DS, reprogram them to become stem cells, and turn them into brain cells in a dish.

In these brain-like cells, researchers have seen Alzheimer-like pathologies develop rapidly. This includes characteristic trio-amyloid plaque-like lesions characteristic of Alzheimer’s progression, progressive neuronal cell death, and abnormal accumulation of a protein called tau inside neurons.

“This study represents a surprising achievement, as it is the first cell-based system to have a complete trio of Alzheimer’s disease without artificial gene overexpression. It opens up the possibility of screening new drugs of interest. Alzheimer’s disease is before neuronal cell death begins.”Dean Nizetick, Principal Investigator at Queen Mary University in London.

Researchers have shown that this system can be used as an early prophylactic drug testing platform. They took two different drugs known to inhibit β-amyloid production, tested them on these brain cells, and showed that at six weeks they prevented the development of Alzheimer’s disease.

Although these two specific drugs didn’t pass clinical trials for other reasons, they aren’t the treatments of choice for Alzheimer’s disease, but the team has demonstrated that the system can be used with any drug compound, and within 6 weeks Further investigation is possible.

The team also found evidence of the existence of a naturally functioning suppressor gene for Alzheimer’s disease, the BACE2 gene. Acts similarly to the tumor suppressor gene in cancer, and the increased activity of this gene contributes to the prevention/deceleration of Alzheimer’s disease in human brain tissue and to determine the risk of people developing the disease in the future. Can be used as a biomarker of, or as a new therapeutic approach by enhancing its action.

“Although it is still in its infancy, this system increases the theoretical potential for further development as a tool for predicting who may develop Alzheimer’s disease. Using the same stem cell process for any hair follicle The idea is to develop Alzheimer’s disease in a dish, the idea of ​​which is a cell-based system that captures people at high risk of early disease before it begins in the human brain, allowing for personalized preventive intervention. There is a long way to go to reach this goal.” Nizetic.

“I think we now have the potential to develop new human models of this disease. This would be a huge step forward,” he added.o-UCL author John Hardy.

The findings in this study depended on the contributions of DS patients who were willing to accept participation in this study, and the results may be beneficial in preventing Alzheimer’s disease with or without DS. The Down Syndrome Society (UK) provided essential support and assistance in recruiting participants for the study.

Reprinted courtesy of Queen Mary University in London.