Alzheimer’s disease has no known cure. Studies suggest that this is because the neurodegenerative condition results from complex interactions between several genetic, lifestyle and environmental factors. Consequently, this has led to challenges in developing a single drug to treat every case of Alzheimer’s disease.
New Study Testing APOE4
A recently published study suggests that the precision medicine approach may be a useful way to scale the drug discovery hurdle. In precision medicine, disease treatment and prevention account for individual variation in genes, environment and lifestyle and accommodate personalization based on the factors that may affect response to treatment.
A new study recently published in the journal Nature Aging by Alice Taubes and colleagues used this method to target specific genes that increase the risk of developing Alzheimer’s disease. Their aim was to investigate potential therapeutic options for its treatment.
They focused on individuals who have the APOE4/4 genotype. Using a computational approach they found that bumetanide was one of their top hits. They hypothesized that drugs that reverse the expression of differentially expressed genes in disease states toward normal levels may be beneficial against the condition.
What is Bumetanide?
Bumetanide is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart, kidney, and liver disease. Bumetanide is in a class of medications called diuretics (‘water pills’). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine.
Bumetanide comes as a tablet to take by mouth. It usually is taken once a day. When used to treat edema, a second or third dose may be given every 4 to 5 hours depending on the amount of swelling.
What Did the Researchers Do?
They first chose the APOE genotype, which is a major risk factor for developing late-onset AD. Next, they analyzed brain tissue samples from people with Alzheimer’s disease to identify the APOE gene expression signatures and bumetanide emerged as a suitable candidate for reversing APOE4-related expressions back to normal levels in individuals with Alzheimer’s disease.
They genetically modified the brains of the rodents to produce APOE4-like symptoms, and they then treated the animals with bumetanide. After which they subjected them to learning and behavioral tests.
They also extend the study to humans by using genetically derived APOE4 neurons from the skin cells of an individual with this genotype.
The researchers found that in the brains of the genetically modified animals, bumetanide significantly reversed the APOE4 signature genes. Also, the medication improved memory formation and restored the ability of neurons to respond to stimuli by reorganizing their function and connections.
They confirmed that those with exposure to bumetanide treatment had a significantly lower prevalence of Alzheimer’s disease than people without exposure to bumetanide treatment.
Their findings led to their conclusion. That bumetanide may be effective in preventing Alzheimer’s disease. Larger scale studies will be needed in order for their results to have clinical implications in human Alzheimer’s disease treatment.
Hassan Yahaya (2021, Oct 28). A water pill may stave off Alzheimer’s by targeting genes responsible for the condition. Medical News Today. Retrieved from: