New drug causes ‘complete loss’ of gained weight without ‘any untoward side effects’

Researchers give obese mice drug packaged inside nanogel and delivered via an injection

Vishwam Sankaran
Wednesday 30 August 2023 06:40 BST
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Scientists have developed a gel-based carrier that delivers a drug exclusively to the liver of obese mice and reverses their diet-induced disease.

Previous studies have shown that thyromimetics – or drugs mimicking the body’s natural thyroid hormone – are a potential way to tackle obesity, which affects over 100 million people worldwide, and other metabolic conditions like Type 2 diabetes.

Targeted therapy is key to achieving this when using such drugs, said researchers, including those from the University of Massachusetts.

They said if the drug was not delivered selectively to the liver, it could “cause complications”.

So scientists worked on developing a novel delivery platform for small and large molecules so the drug got to the right place in the body.

A group of mice were fed a high-fat, high-sugar and high-cholesterol diet for 10 weeks so their weight could be doubled, while a control group of mice was fed a healthy diet for the latest study published recently in the journal PNAS Nexus.

“We came up with a very simple approach, using our unique invention – nanogels that we can direct selectively to different targets, which we call IntelliGels. They were custom-designed for hepatocyte delivery in the liver,” study co-author S Thai Thayumanavan said in a statement.

Researchers gave the obese mice the drug daily – packaged inside the nanogel and delivered via an injection.

“The treated mice completely lost their gained weight, and we did not see any untoward side effects,” Dr Thayumanavan said.

When the nanogel carrier reaches the liver cells, the body’s glutathione enzyme breaks down bonds in the gel, releasing the drug, scientists explained.

This then leads to the drug activating the cells’ thyroid hormone beta receptor, leading to systemic lowering of fat molecule levels in the body, increased bile acid synthesis and fat burning.

Researchers found that after five weeks of treatment, the mice returned to a normal weight – even as their high-fat diet continued.

They also saw the mice’s cholesterol levels drop and their liver inflammation resolve.

“We really wanted to find out the factors that got affected,” Dr Thayumanavan said.

“We found that we are activating the reverse cholesterol transport pathway, which lowers cholesterol. We believe that activation of fat oxidation and an increase in metabolic rate are causing the loss in weight, but more work needs to be done to prove that point,” he said.

While there is a considerable amount of drug development work to be conducted between mice and humans, researchers hope the treatment will eventually become a drug.

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