Credit score: Unsplash/CC0 Public Area
Glucagon-like peptide-1 (GLP-1) receptor agonists are peptide-based therapeutics for treating diabetes and for weight reduction. Sadly, shortages and excessive prices have made it tough for individuals to begin and preserve therapy.
Now, researchers report a drug supply system that “paints” these peptides immediately on the antibodies they aim. In research with mice, the system led to sustained weight reduction and extended blood sugar administration with a GLP-1 injection one fourth that of the usual dose.
Bradley Pentelute, professor of chemistry on the Massachusetts Institute of Know-how (MIT), presents his crew’s outcomes on the spring assembly of the American Chemical Society (ACS 2025) held March 23–27 in San Diego.
Peptide-based therapies are extremely efficient. Nevertheless, they’re simply degraded by enzymes in an individual’s physique as a result of peptides lack the structural stability that bigger, extra advanced proteins have.
A technique that scientists have tried to work round this limitation for GLP-1 receptor agonists is by fusing the peptide on to an individual’s immunoglobulin G (IgG) antibodies. These long-acting, drug-fused IgGs act as wonderful peptide ferries, however they’re expensive as a result of the antibodies have to be extracted and modified in a laboratory earlier than they are often efficient inside that very same particular person’s physique.
Pentelute and his crew have developed a expertise to connect GLP-1 receptor agonists to IgGs throughout the physique. The drug supply system, which he calls in vivo antibody portray, is itself a peptide and consists of a binder area that attaches to the IgG, a payload area that carries the GLP-1 receptor agonist, and a reactive area that attaches (i.e., paints) the GLP-1 drug onto the IgG with a covalent bond.
In laboratory exams of the antibody portray platform on mouse and human IgGs, the researchers discovered that almost half of all antibodies efficiently connected to GLP-1 receptor agonists at a physique temperature of 98.6°F (37°C).
Subsequent, they examined the platform for delivering GLP-1 receptor agonists in a mouse mannequin for kind 2 diabetes and metabolic-induced weight problems. Pentelute and his colleagues discovered that the mice skilled sustained blood glucose administration and weight reduction for as much as 15 days after a single therapy.
Actually, mice that acquired antibody portray had higher and longer-lasting outcomes at a GLP-1 drug dose, a lot decrease than the present historically administered dose.
The researchers have shared their findings in a preprint analysis article on bioRxiv that’s at present beneath peer assessment. Pentelute expands upon this work throughout his ACS Spring 2025 presentation, together with new outcomes from demonstrations exhibiting that the platform can successfully paint antibodies within the presence of extracellular particles resembling mobile proteins.
“We’re also expanding the technology to make antibody drug conjugates for cancer,” shares Pentelute. “And we’re modifying this technology to be able to paint multiple drugs onto one antibody,” he provides. “With new technology like this, the future of peptide-based therapies could see reduced costs and enhanced effectiveness.”
This expertise is included in a pending provisional patent from MIT. Katsushi Kitahara, a research co-author, is employed by a pharmaceutical firm. Pentelute is a co-founder and concerned with a number of corporations specializing in the event of protein and peptide therapeutics.
Extra info:
Katsushi Kitahara et al, In vivo Antibody Portray for Subsequent Technology Weight Loss Medication, bioRxiv (2024). DOI: 10.1101/2024.08.22.609257
Supplied by
American Chemical Society
Quotation:
Enhancing GLP-1 drug supply by ‘portray’ it on antibodies (2025, March 23)
retrieved 23 March 2025
from https://medicalxpress.com/information/2025-03-glp-drug-delivery-antibodies.html
This doc is topic to copyright. Aside from any honest dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is offered for info functions solely.
