More than 100 million Americans struggle with obesity and related metabolic disorders, a staggering number with widespread consequences.
“We were really excited about this work,” says S. Thai Thayumanavan, a biomedical engineer and chemist at the University of Massachusetts Amherst. This technique takes on greater significance when viewed against the broader health crisis.
At the heart of this breakthrough is a tiny yet powerful tool—nanogels. These microscopic carriers hold a synthetic thyroid hormone drug known as a thyromimetic. While thyroid hormones are vital for liver metabolism, their systemic use often leads to severe side effects, making them an unreliable treatment option.
Rather than administering the hormone throughout the body, researchers designed nanogels to deliver it precisely where it’s needed.
“We came up with a very simple approach, using our unique invention—nanogels that we can direct selectively to different targets,” Thayumanavan explains. “They were custom-designed for hepatocyte delivery in the liver.” This precision avoids the harmful effects associated with traditional treatments.
The results were striking. Mice given the treatment lost all the excess weight they had gained, with no harmful side effects. “The treated mice completely lost their gained weight, and we did not see any untoward side effects,” Thayumanavan reports.
But the benefits went beyond weight loss. Despite remaining on a high-fat diet, the mice showed improved cholesterol levels and significantly reduced liver inflammation. The findings suggest a deeper metabolic shift rather than just a temporary fix.
“We found that we are activating the reverse cholesterol transport pathway, which lowers cholesterol,” Thayumanavan explains. This discovery points to a potential long-term solution for obesity-related conditions, offering hope for safer and more effective metabolic treatments.
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He further theorizes, “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.”
Delving into the mechanics, once these nanogels permeate the hepatocytes, the liver cell environment disintegrates the bonds within the nanogel, releasing axitirome. This drug subsequently latches onto proteins pivotal for gene expression regulation.
The apparent effectiveness of the ANG-delivered axitirome, which reversed weight gain without disrupting thyroid hormone levels, indicates a promising avenue for thyromimetics in addressing metabolic diseases like obesity.
An interesting observation emerged: mice on axitirome retained their appetite for high-calorie food. This is in stark contrast to human subjects using other weight loss drugs.
“There is a significant amount of development work to be conducted between mice and humans,” Thayumanavan cautions, “but we are hoping it will eventually become a drug.”
Driven by the promise of the nanogel technology his lab birthed, Thayumanavan has launched a startup, Cyta Therapeutics. Their primary mission? To spearhead cutting-edge delivery platforms ensuring drugs are dispatched to their intended bodily destinations.
The exciting potential of this discovery cannot be understated. It not only offers a beacon of hope for those grappling with obesity and associated disorders but also paves the way for further advancements in drug delivery, potentially revolutionizing the treatment of metabolic diseases.
Thyromimetics are drugs that mimic the effects of thyroid hormones, primarily triiodothyronine (T3), by activating thyroid hormone receptors (THRs). They are being explored for various therapeutic applications due to their ability to regulate metabolism, cholesterol levels, and other physiological functions. Here are some potential benefits of taking thyromimetics:
While thyromimetics have promising benefits, excessive activation of thyroid receptors can cause tachycardia, muscle wasting, osteoporosis, and hyperthyroid-like symptoms.
The key is selectivity, with newer drugs targeting THR-β more than THR-α to avoid these side effects.
Thyromimetics are currently under investigation for their therapeutic potential, especially for cardiovascular and liver diseases.
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