For the first time, a cost-effective and commonly used diabetes drug, Glipizide, can be effectively repurposed for treatment of some devastating human brain disorders such as Huntington’s disease and other poly(Q) disorders, according to researchers at Delhi University’s Genetics department. The study, conducted on Drosophila (common fruit flies) disease models, have shown significant findings that researchers now plan to repeat in mice and other mammals to clear the path for human clinical trials.
The research — ‘Glipizide ameliorates human poly(Q) mediated neurotoxicity by upregulating insulin signalling in Drosophila disease models’ — has been recently published in science journal Biochemical and Biophysical Research Communications (BBRC), apart from Nature India. Researchers have reported for the first time that an insulin stimulating drug ‘Glipizide’ that is already available in the market could help in treating Huntington’s disease and other poly(Q) disorders by oral administration.
Glipizide is a low-cost anti-diabetic drug which is popularly used for the treatment of type 2 diabetes (T2D) mellitus. It is an FDA-approved second-generation sulfonylurea drug which stimulates insulin signalling by promoting insulin secretion and increasing the sensitivity of peripheral tissues towards insulin. Insulin signalling is a critical controller of cellular metabolism and energy homeostasis.
“Experiments were conducted to check if any available drug(s) enhances the level of insulin signalling in the disease affected neuronal cells to restrict progression of Huntington’s disease,” Prof Surajit Sarkar from the Delhi University’s genetics department told The Indian Express. Disorders such as Huntington’s disease and Spinocerebellar ataxia type 3 (SCA3) are incurable human brain illnesses which manifest in the form of severe behavioral and physical impairments. Huntington’s disease is the most common monogenic (single gene driven) neurodegenerative disorder and the commonest genetic dementia of the present time. “It passes down from generation to generation, and if one parent is a carrier of the disease-causing gene, his/her offspring have a 50/50 chance of inheriting the disease. With typically midlife onset, and progressive motor, intellectual and psychiatric symptoms; its impact on patients and their families is truly devastating,” the expert adds.
This strategy is known as drug repositioning or drug-repurposing, which involves identification of novel uses of available drugs/ molecules that are otherwise outside the possibility of the original medical indication. This approach helps in quashing the huge costs and slow pace of new drug discovery and development, Prof Sarkar explained.
While working on the molecular mechanism, Sarkar, along with another study author Shweta Tandon, noted that Glipizide treatment significantly reduces the burden of neurotoxic protein clumps in the brain, causes a remarkable decrease in the death of neuronal cells, and helps in reinstating the functional precision. It appears that Glipizide mediated improved levels of insulin signalling rejuvenates the brain neurons, which were otherwise abrogated due to disease conditions, authors of the study have said. “We have conducted this study on Drosophila (common fruit flies) disease models since the insulin signalling pathway of the insect is very much similar to that of human beings. We will now look forward to validating our findings in mice and other higher mammals to clear the path for human clinical trials,” the researchers added.
