SAN DIEGO, CA -- An international team of scientists, led by Yousef Al-Abed, PhD, a medicinal chemist at the Institute for Medical Research of the North Shore-Long Island Jewish (LIJ) Health System in Manhasset, NY, has identified a gene that plays a critical role in the development of type 1 diabetes. This is the type of diabetes that typically arises in childhood, requires insulin injections for life and can have serious complications like heart disease, kidney disease and blindness. The identification of this gene opens the door to new drugs and gene therapy. Dr. Al-Abed described the team's findings today at the 229th national meeting of the American Chemical Society in San Diego, CA.
The gene is responsible for making an immune system messenger called macrophage migration inhibitory factor (MIF), a protein that the scientists previously showed to be significantly elevated in the insulin-producing cells of the pancreas. Last year, the same team reported on a compound developed by Dr. Al-Abed that blocked MIF and the development of diabetes in laboratory experiments.
When injected into mice treated with a chemical known to induce a form of type 1 diabetes, the compound completely protected them from developing the disease. All of the mice given only the diabetes-inducing chemical and not the compound treatment developed the disease. In a similar experiment, the compound was injected into mice that were genetically bred to develop diabetes and 90 percent of them did not develop the disease.
In the new experiments, the team gave the diabetes-inducing chemical to mice that they specially bred to lack the MIF gene and found that they were resistant to developing diabetes. Dr. Al-Abed notes the uniqueness of their findings: Other teams have studied other immune system messengers through this method of gene deletion and none were found to play a role in the development of the disease.
Type 1 diabetes afflicts approximately one million people in the United States and studies show that it is on the rise worldwide. The disease is caused by an inability of the body to make insulin. Normally, insulin is manufactured in the pancreas in cells called "beta cells." In people with type 1 diabetes, something triggers the immune system to attack and kill the beta cells, so that insulin can no longer be made. That trigger is unknown, but viruses, foods and genes have all been suspected of playing a role.
"We've shown that the MIF gene is crucial for the development of type 1 diabetes," said Dr. Al-Abed. The scientists believe that MIF plays a major role in the cascade of immune system events that leads to the destruction of the beta cells. In prediabetic individuals, blocking the protein would halt the harmful immune process and leave the remaining beta cells intact and able to produce insulin. "While it's very likely that multiple genes are involved, our findings provide evidence that blocking this particular protein is a promising approach for fighting diabetes," Dr. Al-Abed added.
The scientists are conducting other experiments with the compound to determine if it may be helpful as a treatment for already-existing cases of type 1 diabetes and the more common form of the disease, type 2 diabetes, which affects an estimated 16 million Americans. Developing the compound into a long-acting oral drug for people and testing its safety and effectiveness would take years, the scientists caution, as would gene therapy.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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