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Chemists identify key gene in development of type 1 diabetes


Chemists say they have identified a gene that appears to play a key role in the development of type 1 diabetes, also known as insulin-dependent or juvenile diabetes, a disease that affects about one million people in the U.S. and is on the rise worldwide. They described their findings, which they say could lead to new drug interventions and possibly gene therapy, today at the 229th national meeting of the American Chemical Society, the world’s largest scientific society.

In the current study, the researchers focused on the formation of the MIF protein (macrophage migration inhibitory factor), a proinflammatory protein that they showed in previous studies is elevated in diabetic animals and may be involved in the cascade of immunological events that leads to the destruction of the pancreas and the subsequent onset of type 1 diabetes. The disease is much less common than type 2 diabetes, formerly known as adult onset or non-insulin-dependent diabetes, which is often associated with obesity.

"We’ve shown that the MIF gene is crucial for the development of type 1 diabetes," says study leader Yousef Al-Abed, Ph.D., a chemist at the Institute for Medical Research of the North Shore-Long Island Jewish (LIJ) Health System in Manhasset, N.Y. "It is not the only factor involved in this complex disease, but it is certainly a promising target for its prevention and treatment."

In preliminary studies by the research group, specially bred mice that lacked the gene for the MIF protein failed to develop diabetes compared to mice that possessed the gene, according to the investigators. Although it’s likely that multiple genes are involved in the formation of diabetes, the finding provides proof of concept that efforts to block the formation of this particular protein is a promising approach for fighting diabetes, they say.

"The MIF gene may be regulating other genes involved in type 1 diabetes," says Al-Abed. "We don’t know yet, but we’re looking into this." Besides drug intervention, the new finding could lead to gene therapy to prevent the disease, possibly by disrupting the network of genes involved in its development, he says.

A potential drug treatment based on blocking the MIF protein is already being explored. In a study presented last year at an ACS national meeting, the researchers reported they were able to prevent diabetes in a group of mice by using a synthetic compound called ISO-1 to block the MIF protein. If human studies prove the effectiveness of ISO-1, the compound or its derivatives could ultimately save lives, reduce health care costs and help prediabetic people, particularly children, avoid a lifetime of insulin injections, Al-Abed says. Prediabetic individuals are those who have blood markers — either antibodies or genetic markers — that are predictive of the disease but are still able to produce insulin.

Al-Abed and his associates hope that the experimental compound can one day be developed into a long-acting oral drug that could be taken by prediabetic people to achieve lasting protection, perhaps a lifetime. But such a drug would take years to develop and test, the researchers caution. Likewise, effective gene therapy against the disease may take many years to develop, they add.

Besides prevention, ISO-1 also is being tested in animals to determine whether it will help in the actual treatment of ongoing type 1 diabetes and type 2 diabetes, the more common type. Results are not yet available from these tests, the researchers say.

Although nobody knows the exact cause of type 1 diabetes, and there is no cure, the disease can be controlled and its complications minimized by following a healthy diet, getting exercise and taking prescribed medications as directed, according to health experts.

The Institute for Medical Research at North Shore-LIJ provided funding for this study.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

Michael Bernstein | EurekAlert!
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