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T2DM breakthrough

New approach for T2DM treatment

2H10 monoclonal antibody enhances glucose tolerance
Professor Ulf Eriksson

Blocking the signal of the VEGF-B protein that prevents fat from accumulating in muscles and in the heart could be the key to enabling these tissues to respond to insulin and thereby create an entirely new approach to the treatment of T2DM.

Reporting in the journal Nature, an international team of scientists led from Karolinska Institutet, Sweden, prevented the development of T2DM and reversed the progression of established disease In experiments on mice and rats. They concluded that a VEGF-B antagonism could be used as a novel pharmacological approach for type 2 diabetes.

“We discovered VEGF-B back in 1995, and since then the VEGF-B project has been a lengthy sojourn in the wilderness, but now we're making one important discovery after the other,” said Professor Ulf Eriksson, Department of Medical Biochemistry and Biophysics at Karolinska. “In this present study we've shown that VEGF-B inhibition can be used to prevent and treat type 2 diabetes, and that this can be done with a drug candidate.”

Insulin resistance is related to the storage of fat in the 'wrong' places, such as the muscles, blood vessels and heart. Although it is not fully known why insulin resistance is related to the storage of fat, it has been previously reported that the VEGF-B protein affects the transport and storage of fat in body tissue.

Pharmacological inhibition was enabled by utilising 2H10, is a monoclonal antibody, developed by the biopharmaceutical company CSL Limited. Mice that were administered the antibody resulted in enhanced glucose tolerance, preserved pancreatic islet architecture, improved β-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome.

The potential use of VEGF-B neutralisation in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalised insulin sensitivity and increased glucose uptake in skeletal muscle and heart.

Åke Sjöholm

“The results we present in this study represent a major breakthrough and an entirely new principle for the prevention and treatment of type 2 diabetes," said Professor Åke Sjöholm, consultant in diabetology at Stockholm South General Hospital. “Existing treatments can cause many adverse reactions and their effects normally wear off. There is a desperate need for new treatment strategies for type 2 diabetes.”

A total of four related studies are reported in the Nature paper. In another two studies, the scientists took normal mice and rats that had not been specially bred to develop type 2 diabetes, and left them to develop the disease as a result of a fat-rich diet and the resulting obesity. In these cases, progression of the established disease was halted and reversed to varying degrees after treatment with 2H10.

Earlier in 2012, Professor Eriksson was awarded a SEK15 million (£1.4 million) research grant, which will be used to finance further research into VEGF-B.

The findings are the result of a joint effort by Karolinska Institutet, the Ludwig Institute for Cancer Research and the Australian biopharmaceutical company CSL Limited, amongst others.

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