June 25, 2024

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Innovative Drug Reverses Obesity with Preliminary Testing Showing No Side Effects

Innovative Drug Reverses Obesity with Preliminary Testing Showing No Side Effects

Innovative Drug Reverses Obesity with Preliminary Testing Showing No Side Effects

A biomedical engineer at the University of Massachusetts Amherst has employed a nanogel carrier designed in their laboratory to deliver a drug specifically to the livers of obese mice, effectively reversing the diseases caused by their diet. S. Thai Thayumanavan, a distinguished professor of chemical and biomedical engineering, stated, “The treated mice shed all their added weight, and we found no adverse effects. Considering that 100 million Americans suffer from obesity and related metabolic diseases, we are very excited about this work.”

Breakthrough Findings and Future Potential

Leveraging Thayumanavan’s laboratory nanogel technology, the Massachusetts Institute of Applied Life Sciences (IALS) has established a new startup company called Cyta Therapeutics, which is working to translate these research findings for human use. In late July, Cyta Therapeutics won the “Judges’ Choice Best Startup Company” award at the 16th Massachusetts Life Sciences Innovation (MALSI) conference held in Boston.

S. Thai Thayumanavan is a distinguished professor in the Department of Chemical and Biomedical Engineering at the University of Massachusetts Amherst. Source: University of Massachusetts Amherst

Thayumanavan remarked, “There is still a lot of development work to be done between mice and humans, but we hope it eventually becomes a drug.”

The senior author of the paper, IALS Center for Bioactive Delivery Director Thayumanavan, explained his team’s research findings in a paper published on August 29th in the journal “PNAS NEXUS.” Ruiling Wu, who recently earned her Ph.D. in chemistry at the University of Massachusetts, conducted the research in Thayumanavan’s lab and is the first author of this paper. Wu now works at a pharmaceutical company in Boston.

Addressing Metabolic Issues through Targeted Delivery

One of the main goals of the center is to study how to create new delivery platforms for both small molecules and large molecules to deliver the right drugs to the right places in the body.

Thyroid mimetics, drugs that simulate synthetic thyroid hormones, have long been considered a potential approach to addressing obesity, type 2 diabetes, high cholesterol, metabolic dysfunction-associated fatty liver disease (MAFLD), and other metabolic diseases. However, targeted therapy is key. Thayumanavan and his team studied one such thyroid mimetic drug.

Innovative Drug Reverses Obesity with Preliminary Testing Showing No Side Effects

After delivering the thyroid mimetic drug directly to the livers of obese mice using nanogel carriers, diet-induced obesity was reversed. Source: Thayumanavan Lab, University of Massachusetts Amherst

“We realized that we need to selectively deliver this drug to the liver because delivering it elsewhere could lead to complications. Besides the side effects, systemic delivery would dilute the drug’s efficacy, which was confirmed in our research,” he said.

Research Approach and Results

Thayumanavan and his team fed a group of mice a high-fat, high-sugar, high-cholesterol diet for ten weeks, causing their weight to double. The control group of mice consumed a healthy diet.

“We came up with a very simple way using our unique invention – nanogels that we can selectively guide to different targets, which we call IntelliGels. They are custom-designed for delivering to liver cells,” he said.

Researchers injected the obese mice with the drug daily, which was packaged within nanogels and administered to the mice through intraperitoneal injection (IP). Once the nanogel carrier entered liver cells, glutathione within the cells would break the bonds in the nanogel, releasing the drug. The drug would then activate thyroid hormone beta receptors, leading to reduced body fat, increased bile acid synthesis, and fat oxidation throughout the body. After five weeks of treatment, the mice returned to a normal weight, even as they continued their high-fat diet. Cholesterol levels in the mice also decreased, and liver inflammation improved.

“We are trying to figure out the factors involved,” Thayumanavan said. “The latest finding is that the drug activates the cholesterol reverse transport pathway, leading to lower cholesterol. The activation of fat oxidation and increased metabolic rate is likely the reason for the weight loss, but more work is needed to prove this.”

The paper notes that with a better understanding of this mechanism, “drug-encapsulated nanogels offer the possibility of nanoparticle-mediated drug delivery strategies for treating other liver diseases.”

Innovative Drug Reverses Obesity with Preliminary Testing Showing No Side Effects

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