A research team from MIT has developed a groundbreaking drug delivery system that could potentially solve the persistent shortages of GLP-1 medications like Ozempic and Wegovy by significantly reducing the amount of medication needed for effective treatment.
The innovative approach, called "peptide painting," was presented at the recent American Chemical Association meeting by a team led by Bradley Pentelute, professor of chemistry at MIT. Their findings demonstrate that this improved delivery method could maintain therapeutic efficacy while using just one-fourth of the typical GLP-1 dose.
Breakthrough in Peptide Delivery Technology
In mouse studies, the researchers found that their novel delivery system resulted in sustained weight loss and extended blood sugar management with dramatically lower doses than conventional GLP-1 injections. Most remarkably, the effects persisted for up to 15 days after a single injection.
"We're also expanding this technology to make antibody drug conjugates for cancer. And we're modifying this technology to be able to paint multiple drugs onto one antibody," said Pentelute in a press release. "With new technology like this, the future of peptide-based therapies could see reduced costs and enhanced effectiveness."
The technology addresses a fundamental challenge with peptide-based therapies like GLP-1 receptor agonists, which, despite their effectiveness, are easily degraded by enzymes in the body due to their lack of structural stability compared to larger proteins.
How the 'Painting' Process Works
The innovative delivery system, termed "in vivo antibody painting," attaches GLP-1 receptor agonists directly to immunoglobulin G (IgG) antibodies within the patient's body. This represents a significant improvement over existing approaches that require extracting and modifying antibodies in a laboratory before reintroduction to the patient—a costly and complex process.
The technology consists of three key components: a binder region that attaches to the IgG, a payload region carrying the GLP-1 receptor agonist, and a reactive region that "paints" the GLP-1 drug onto the IgG with a covalent bond.
Laboratory tests demonstrated impressive efficiency, with nearly half of all antibodies successfully attaching to GLP-1 receptor agonists at normal body temperature (98.6°F/37°C). When tested in mouse models of Type 2 diabetes and metabolic-induced obesity, the platform showed superior and longer-lasting results compared to traditional GLP-1 administration methods.
Addressing Critical Medication Shortages
The timing of this technological advancement is particularly significant given the widespread shortages of GLP-1 medications that have made it difficult for patients with Type 2 diabetes and obesity to receive consistent treatment.
By potentially reducing the required dosage to one-fourth of current levels while maintaining or even improving therapeutic outcomes, the technology could help alleviate supply constraints while potentially reducing treatment costs.
Future Applications Beyond Diabetes and Obesity
The research team is already looking beyond diabetes and weight management applications. Pentelute revealed that they are expanding the technology to create antibody drug conjugates for cancer treatment and developing modifications that would enable multiple drugs to be painted onto a single antibody.
The researchers have shared their findings in a preprint research article currently under peer review, with funding provided by Pentelute's discretionary funds at MIT and the National Cancer Institute at the National Institutes of Health.
Implications for Peptide-Based Therapies
This technological breakthrough could represent a paradigm shift in how peptide-based medications are delivered. By overcoming the inherent instability of peptides in the body, the painting technology might open new possibilities for a wide range of therapeutic applications beyond GLP-1 medications.
For patients struggling with diabetes and obesity, this innovation offers hope for more accessible and effective treatment options in the future, potentially transforming the landscape of metabolic disease management.
