Antibodies against diabetes and obesity

Newly developed antibody counteracts diabetes and obesity

30.11.2012

Successful treatment of diabetes and obesity with an antibody developed in the laboratory possible? Canadian and American researchers have in the trade magazine „Science Translational Medicine“ published a study in which they tested the use of a new antibody in monkeys. The result was convincing: The overweight animals lost significantly in body weight, their blood lipid levels fell, the blood sugar level and insulin levels improved. There is hope for a new approach to treating obesity and diabetes in humans, according to researchers led by Ian Foltz, Sylvia Hu and Chadwick King of the genetic engineering company Amgen in British Columbia. They were supported in their research by scientists from Texas A & M University in Houston.

It has been known for some time that Fibroblast Growth Factor 21 (FGF21) has a far-reaching effect on the regulation of blood sugar and blood lipid levels. For example, previous studies have shown that genetically engineered mice that produced more FGF21 did not have an elevated body fat percentage or signs of diabetes, even with high-fat foods. The FGF21 binds at certain docking sites in the cell walls of the pancreas, the adipose tissue and the liver and thus unfolds its regulatory effect, write Foltz and colleagues. However, it was not possible to use FGF21 directly as a drug, because the hormone in the blood too quickly disintegrate. Therefore, the researchers developed in the laboratory the antibody mimAb1, which occupies exactly the same docking site as FGF21. In experiments with macaques (subtype of macaques), the researchers then tested whether mimAb1 also in terms of body weights, the blood lipid, insulin and blood sugar levels of the animals, the same effect as FGF21.

Improving blood levels and reducing body weight
All monkeys were heavily overweight before the study, but otherwise healthy, the researchers write. The scientists twice intravenously injected a solution of the mimAb1 antibody into half of the 20 experimental animals, the remaining animals served as a control group and received only one saline solution. The researchers then weekly checked body weight, blood lipid blood sugar and insulin levels. „In obese cynomolgus monkeys, injection of mimAb1 resulted in FGF21-like metabolic activity, including reduction in body weight, insulin, triglycerides, and glucose in blood plasma“, write Foltz and colleagues. Five to six weeks after the administration of mimAb1, the body weight of the monkeys was according to the researchers „dropped by around ten percent.“ The animals showed during this time also a significant reduction of the waist circumference. The effect lasted up to nine weeks after the injection. The also observed improvement in blood lipid levels decreased after about seven weeks.

New treatment approach for diabetes and obesity
The monkeys showed a reduction in body weight and an improvement in blood levels, although they did not eat much less than usual, which suggests that the antibody increases energy consumption and thus promotes fat burning, the researchers report. The side effects were hardly observed in the animals during the experiments, because mimAb1 with its molecular structure docks highly specific only at the FGF21 receptors, so Foltz and colleagues. The newly developed antibody has comparable positive effects on the metabolism as FGF21, but its structure is stable, making its use as a drug possible, the researchers write. Now, the new must „innovative therapeutic approach against diabetes and obesity“ be reviewed in further studies. (Fp)

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Image: Martin Gapa