The Pharmaceutical Journal
Vol 272 No 7294 p441
10 April 2004

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Compound offers new direction in prevention of type 1 diabetes

ISO-1, a synthetic compound, has shown promise as a chemopreventive agent in type 1 diabetes. The compound, identified by researchers at North Shore-Long Island Jewish Research Institute in Manhasset, New York, is thought to work by blocking a protein called macrophage migration inhibitory factor (MIF). This protein is a cytokine involved in the regulation of the immune system. Its role in diabetes has not been thoroughly explored but it is known that the cascade of inflammatory events can lead to the destruction of pancreatic beta cells and eventually to the onset of diabetes.

Over a 10-day period the researchers administered ISO-1 to mice injected with a chemical to induce type 1 diabetes and found that the compound protected the mice from developing the disease. In another experiment, ISO-1 was given via injection to mice that were genetically susceptible to diabetes. The compound prevented onset of diabetes in 90 per cent of the treated mice, the researchers say.

In both groups of treated mice, insulin continued to be produced and the mice did not show signs of adverse effects.

“We believe this is the most promising compound to date for preventing type 1 diabetes,” said Yousef Al-Abed, one of the study investigators. “If it works it will be especially beneficial for young people, who often have a difficult time managing their diabetes with daily insulin injections.”

Dr Al-Abed adds that, because ISO-1 is a relatively small chemical compound, it could be developed into an oral drug that functions like a vaccine. Data from the study show that the benefits of ISO-1 treatment were long-lasting, with mice being protected from developing the disease for up to two months after the treatment was stopped.

The data were presented at the 227th national meeting of the American Chemical Society last week.

ISO-1 — (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester — is also being tested in animals to determine whether it can be used as a treatment for both type 1 and type 2 diabetes.