For decades, Alzheimer’s research has focused on examining amyloid plaques in the brain and prescribing antibody therapeutics that remove the plaques to slow cognitive decline in patients. Now, Emory University researchers from Thota Ganesh’s lab are looking instead at inflammation in the brain – also known as neuroinflammation – and how it contributes to cognitive decline. Neuroinflammation and neurodegeneration both contribute to cognitive deficits, and the goal of Ganesh’s research is to target neuroinflammation to improve cognitive and memory function.
“Unlike antibody therapy, the premise for our grant is to examine small molecule drugs that can either prevent or mitigate the development of Alzheimer's Disease,” says Thota Ganesh, associate professor of pharmacology and chemical biology at Emory University’s School of Medicine. “Our grant from the NIH will take us one step closer to a cure that could help the 55 million people worldwide that are suffering from Alzheimer’s.”
Area covered by inflammatory microglia in the brain of Alzheimer’s disease mice without (left) and with EP2 targeting drug treatment (right).
To date, research in Ganesh’s lab has found that specific molecules targeting EP2 receptors could be beneficial to dampening inflammation in the brain, which would treat early symptoms of Alzheimer’s. With the grant, he intends to develop a preclinical drug candidate for Alzheimer's treatment.
“With this promising new approach, we’re moving toward treatments that target inflammation and offer real hope for slowing the progression of Alzheimer’s disease – as well as other forms of dementia, since inflammation appears to be common across neurodegenerative diseases,” says Allan Levey, a collaborator on this project and founding director of the Emory Goizueta Brain Health Institute and Goizueta Alzheimer’s Disease Research Center. “The impact on patients and families could be profound, and we are optimistic that this work will bring us more effective treatments."
The small molecule drugs will provide long-term, sustainable, and complementary treatment options compared with antibody drugs, and also have potential cost advantages and ease of administration.
“In the first two years of the grant, we will test the two EP2 antagonists in Alzheimer's disease models, select the best drug candidate, and develop a dosing regimen and therapeutic index,” says Ganesh. “Then, over the next three years, we will conduct IND enabling studies on a candidate drug for a phase one clinical trial.”
Researchers are making progress understanding the disease and its biomarkers. And focusing on a small molecule drug treatment could be a gamechanger for the therapeutic landscape of Alzheimer’s. Alzheimer's care cost the U.S. amounts to about $360 billion per year, which could triple by 2050. With that amount of burden on the healthcare system, it’s critically important to find small molecule drugs that are not only more effective at treating patients but scalable for drug manufacturers.
“We need sustainable treatments, and small molecule drugs could get us there,” says Ganesh. “We expect by developing these drugs, we can slow the progression of Alzheimer’s or even cure it entirely. That’s the ultimate hope for our research.”