Science Translational Medicine: Antibodies Take Aim at Diabetes

Antibodies can affect signaling by membrane receptors such as FGFR1 in multiple ways. They can link receptors; target receptor/co-receptor complexes; activate individual receptor splice variants; target proteins that modulate receptor function; or bind to and fine-tune receptor activation.

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[Image: B. Strauch/Science © 2011 AAAS]

Researchers have developed antibodies that fight high blood sugar in mice, according to a new study in the 14 December issue of the journal Science Translational Medicine. These proteins could potentially be used to develop new drugs for type 2 diabetes, a condition that develops when the pancreas stops making insulin or when the body stops responding to insulin.

Without an adequate supply of insulin, the body is unable to haul sugar out of the bloodstream and into cells that use the sweet stuff for energy. Instead, sugar builds up in the bloodstream and wreaks havoc on the heart and blood vessels, nerves, eyes, and even skin.

At the molecular level, type 2 diabetes is linked to a family of fibroblast growth factor or FGF proteins and their receptors. Some of these growth factors, including a molecule called FGFR1, show promise for reversing obesity and other diseases related to diabetes. FGFR1 is a growth factor receptor residing in the pancreas and in fat tissues.

“Our work has defined FGFR1 as a compelling target for antibody-based therapeutics for type 2 diabetes,” said Junichiro Sonoda, senior author of the study and scientist and Genentech Inc.

Previous studies have shown that overweight, diabetic mice treated with a growth factor protein called FGF21 regained normal metabolism and lost weight (without spending hours on a treadmill); yet attempts to use this fat-burning protein in humans have failed.

In the current study, Sonoda and colleagues developed antibodies that mimic FGF21 by binding to FGFR1. Within one week, the blood sugar of diabetic mice who received antibody injections dropped to near-normal levels—without any harmful side effects—compared with diabetic mice who received a nonspecific control antibody.

The treatment also helped diabetic mice lose weight, indicating that FGFR1 plays a role in both diabetes and obesity. Importantly, these antibodies are easily produced and remain active in the body for long periods of time, making them promising candidates for future clinical trials in patients struggling with type 2 diabetes.

“Anti-FGFR1 antibodies will represent a novel class of insulin sensitizers with true disease-modifying properties,” Sonoda said. “We are working to further improve the properties of the antibody for clinical testing.”

Nadia Ramlagan

14 December 2011