Possibly Impossible: Research Team Searches for a New Diabetes Treatment

A person with Type 2 diabetes already has high blood sugar and trouble processing insulin. They also have an abundance of the PTP1B enzyme, perpetuating these issues. By shutting down PTP1B, Trivedi and Dr. Priefer hope the insulin receptors will stay open, encouraging the cells to absorb the sugar from the bloodstream.

“I have successfully synthesized a dozen compounds so far,” Trivedi explained. “I’ll continue to synthesize more while testing the effectiveness of each on the PTP1B enzyme.”

Dr. Priefer, Associate Dean of Graduate Studies in the School of Pharmacy, uncovered the possibility of targeting the PTP1B enzyme by accident while cleaning out a storage room of chemical compounds at a previous job.

“I tested over 150 compounds, and three of them came back with a possible hit for the PTP1B enzyme,” he explained. “When I came to MCPHS, I tasked a graduate student to make variations of those three just to see what would happen. She ended up making a library of 25 compounds, three of which worked well. Brinda’s job is to expand on that work and make as many more variations as she can.”

Trivedi has been doing so for the better part of the last two years. In addition to synthesizing new compounds, she’s also testing them to see how effective they would be against the PTP1B enzyme. Last year, she received a mini grant from the Center for Research and Discovery, which she used to purchase the testing kits.

She moves through the lab with confidence and ease, collecting her materials and preparing her tests. An aspiring scientist, Trivedi earned her bachelor’s degree in pharmacy in India, then came to MCPHS for the specific focus on medicinal chemistry and the opportunity for hands-on lab experience.

“It’s fascinating to learn about how drugs work inside the body,” she said. “Sometimes, just a small quantity of a compound can work miracles.”

Discovering a compound that shuts down the PTP1B enzyme would be a miracle on its own. Dr. Priefer explained that the enzyme is very similar to another found in T cells, which are a critical part of the immune system. The challenge is selectivity, or finding a compound that only affects PTP1B.

“There are others in academia and probably in industry working on this, but the selectivity is a significant problem,” Dr. Priefer said. “It may be an impossible task, but it doesn’t mean we’re not going to try.”

This curiosity is what drives many scientists, he added, and is what ultimately leads to pharmaceutical breakthroughs. If they are successful in their efforts, Dr. Priefer said this compound could have significant benefits compared to GLP-1 medications, including fewer side effects and easier delivery via a pill.

More important than the small chance of discovery, he said, is the experience Trivedi and other graduate students pursuing research projects at MCPHS will gain.

“The bigger picture is for Brinda to advance her skills and use cutting-edge instruments that she will encounter in the real world,” he said. “This tangible experience sets our students apart when they start looking for jobs.”

“I have grown as a person while working in the lab,” Trivedi added. “I’ve become more independent, patient, and gained a better understanding of chemical reactions because of this work.”

The search for a compound to target the PTP1B enzyme will likely continue long after Trivedi has graduated from MCPHS. She said she hopes to work in the pharmaceutical industry one day, focusing on developing other novel compounds.

“Diabetes and cancer are deep, complicated subjects because the most effective medications can be different in every person,” she said. “That’s something I find very interesting and hope to explore.”