With a grant from the National Institutes of Health, Hegde is working toward new treatment options for the disease that claimed his father’s life.
Eight years ago, Vijay Hegde began studying the connection between diabetes and Alzheimer's disease.
When he began as an assistant professor in Texas Tech University's Department of Nutritional Sciences, Hegde's focus was a natural progression of the work that brought him there.
But his research took a dramatically personal turn after his own father was diagnosed with Alzheimer's disease.
Now, three years after his father's death, Hegde is more determined than ever to find a treatment for Alzheimer's disease and help families like his. He's also closer than ever.
Going viral
Hegde remembers his father as a hardworking, ambitious man. He worked for the Federal Reserve Bank in India and, at the time of his retirement, was managing director of the currency printing press.
Hegde was equally driven to succeed. He left India in 1993 after earning his master's degree from the University of Mumbai, and headed to the United Kingdom to pursue his doctorate in molecular biology and biotechnology. Over a decade later, while working at the Pennington Biomedial Research Center in Baton Rouge, Louisiana, Hegde crossed paths with internationally renowned obesity expert Nikhil Dhurandhar.
In the early 1990s, while in Mumbai, India, Dhurandhar began a line of research many scientists of the time scoffed at. He eventually found evidence that a particular virus, adenovirus 36 (Ad36), was causing obesity. Then, Dhurandhar reached a puzzling realization: despite their obesity, those infected with the virus actually experienced improved glucose metabolism. Eventually, he identified a single protein within the virus that was causing this favorable effect. The protein, called E4orf1, became the basis of nearly all of Dhurandhar's future work.
“The COVID-19 pandemic over the past year has made most people consider viruses to be our enemies, causing illness and harm to humans,” Hegde acknowledged. “However, there are many surprising advantages. Viruses have honed advantageous skills over billions of years of evolution to invade and hijack the cellular machinery of living organisms, including bacteria, fungi, animals and, importantly, humans. As such, this ability to manipulate life has enabled researchers to gain insights into how best to exploit this advantage for good.
“Properties of viruses that might have a beneficial purpose have previously been used for therapeutic drug target development for treatment of different cancers. In recent years, the biotechnology and pharmaceutical industry has invested many resources to convert viruses to be beneficial to human health and serve as valuable allies in the fight against other harmful illnesses.”
Spurred on by his passion for chronic disease research, Hegde joined Dhurandhar in studying E4orf1 while at Pennington Biomedical. Then, in November 2014, Dhurandhar became chair of the newly created Department of Nutritional Sciences at Texas Tech. To continue his work, Hegde went with him.
Alzheimer's disease
The research was incredibly complex, so much so that Hegde had trouble fully explaining it to his father.
“He was aware I was involved in biomedical research but did not fully understand the specifics,” Hegde noted. “He obviously never knew the research I was involved in would have a deep connection with him.”
But it did.
“Over the last several years, studies have suggested an association between diabetes and Alzheimer's disease,” he explained. “These studies highlighted that people with diabetes, especially Type 2 diabetes, are at a higher risk of eventually developing Alzheimer's disease or other dementias. In trying to better understand the connection between Alzheimer's disease and diabetes, research showed that the link may be a result of the complex ways Type 2 diabetes affects the ability of the brain and other body tissues to use glucose and respond to insulin.
Because their lab had already proven E4orf1's ability to improve glucose uptake, Hegde and Dhurandhar began to question whether the protein could have a therapeutic use in treating – or even preventing – Alzheimer's disease.
Then came the news Hegde never imagined: His father had been diagnosed with the very disease he was seeking a treatment for. Sadly, the research wasn't far enough along at that point to make a difference for his father, but his father's battle made all the difference for Hegde.
“Seeing the personality changes in my dad because of Alzheimer's disease gave me an insight into how this progressive disease affects a person and his memory,” he said. “So ironically, my dad's disease helped me understand the disease and its effects rather than me helping him. But it did give my research even more meaning, knowing that it could help the many families that are affected by Alzheimer's disease.”
Seeking a solution
Now, with a two-year, $410,807 grant from the National Institutes of Health (NIH), Hegde, Dhurandhar and their colleague Arubala Reddy, a research assistant professor, hope to finally understand the interaction between Type 2 diabetes and Alzheimer's disease.
“Alzheimer's disease is a progressive neurodegenerative disease, and even though several studies have identified Type 2 diabetes as a risk factor for developing dementia attributable to Alzheimer's disease, clinical trials with anti-diabetic agents – though promising – have not been highly effective against Alzheimer's disease,” Hegde said. “To fill this gap and find effective treatments, we need to establish a mechanistic link between the two medical conditions, confined to specific regions of the body: the brain for Alzheimer's disease and the liver and adipose tissue for Type 2 diabetes.
“As the previous treatments were focused only in the periphery or the brain, we wanted to ask the question if treating glucose and insulin impairment concurrently, both in the periphery and the brain, would have better therapeutic outcomes.”
One hallmark of developing Alzheimer's disease is chronic hyperinsulinemia – the presence of abnormally high insulin levels in the blood. Because of E4orf1's ability to reduce high insulin levels, the researchers believe it could help slow, or even stop, the development of Alzheimer's disease.
“I hope this research will be a previously unidentified therapeutic approach,” Hegde
said,
“and help modify currently available therapies or identify new options for prevention
and better clinical management of Alzheimer's disease.”
And with this research, hopefully, in the very near future, fewer families will have to go through what Hegde's did.
