Helps Those with Genetic Predisposition to Alzheimer’s
The gene most strongly linked to Alzheimer’s disease is APOE4, with an estimated 20 to 25 percent of carriers going on to develop the disease. To seek out a drug that might help these people, scientists at the University of California, San Francisco, turned to precision or “personalized” medicine. The idea of this approach is to tailor prevention and treatment strategies by considering individual variations in a person’s genes, environment, and lifestyle. The team began by analyzing 213 samples of human brain tissue to identify how to mitigate the expression of APOE4. They did this by seeking out gene expression signatures – the levels to which genes are turned on or off, specific to APOE4 carriers. Once they found the signatures, they used drug repurposing software to compare them to the gene expression signatures of over 1,300 drugs. Five drugs stood out as being candidates, with the strongest being bumetanide. Then came the laboratory testing…Reduces Memory Loss in Mice
To confirm bumetanide as a drug that might help sufferers with the disease, the scientists performed experiments using human cell lines and laboratory mice. In mice engineered to express the human APOE4 gene and display Alzheimer’s-like symptoms, bumetanide improved memory formation and neuronal excitability – the ease with which the cell responds to a stimulus, a process that’s critical to neuron survival. Bumetanide also improved plasticity – the ability of a brain cell to change activity in response to stimuli by reorganizing its structure, functions, or connections. In cognitive tests, the drug greatly improved learning and memory deficits in the mice. What’s more, the scientists were able to validate these results in human brain cell experiments. During these tests the scientists witnessed a reversal in APOE4 signature genes in a similar manner to what they saw in their first tests with mice. Furthermore, they found three similar signature pathways for expressing the gene in both human and animal brain cells, suggesting patients already taking bumetanide should have a lower risk of Alzheimer’s disease.Up to 75 Percent Reduction in Alzheimer’s Disease
When scientists examined electronic health record data of over five million people over the age of 65 who took bumetanide, as well as a matching group that didn’t take the drug, they were thrilled with the results. They discovered that patients with a genetic risk for Alzheimer’s disease who took bumetanide had between a 35 percent and 75 percent lower prevalence of Alzheimer’s compared to patients not taking the medication. The study, published in the journal Nature Aging in October, was funded by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). NIA Director Richard J. Hodes, M.D., commented, saying “Though further tests and clinical trials are needed, this research underscores the value of big data-driven tactics combined with more traditional scientific approaches to identify existing FDA-approved drugs as candidates for drug repurposing to treat Alzheimer’s disease.” If further validation of the research proves successful, human trials are expected to follow. This is certainly exciting news for those of us who have a genetic predisposition to this terrible disease. I’ll keep you updated on any new findings.