Experimental Drug Slows Type 1 Diabetes

Immune System Tolerance Slows Destruction of Insulin-Producing Cells

From the WebMD Archives

March 29, 2004 -- A novel drug designed to slow or even stop the progression of type 1 diabetes is showing promise in its first limited human trials. Eighteen months after treatment with the experimental drug Diamyd, a small group of patients was better able to produce insulin than patients who did not receive the drug.

At the International Diabetes Society conference in Cambridge, England, researchers reported that seven of eight patients with newly diagnosed latent autoimmune diabetes in adults (LADA), or type 1.5 diabetes, were still producing insulin a year and a half after treatment with Diamyd. Only about half of those patients who did not receive the drug were still producing insulin.

Type 1 diabetes is related to the immune system's destruction of cells that produce insulin. LADA is an adult form of the disease in which the immune system attack occurs later in life in people thought to be susceptible because they have antibodies to the pancreas detectable within the blood.

In the study presented at the conference, insulin production increased by an average of 50% among those who received Diamyd, and the responses were sustained, according to the president of the Swedish company that is developing the drug.

"For the first time we have shown that there is a chance that we can not only treat type 1 diabetes, but prevent it from occurring," Diamyd Medical's Anders Essen-Moller tells WebMD.

But a diabetes expert tells WebMD that much larger studies are needed to prove the experimental drug is effective.

"This is on the list of therapies that has not been tested fully in people yet, and it is hard to say how promising it is until more studies are done," says American Juvenile Diabetes Foundation chief scientific officer Robert Goldstein, MD.

Protect From Attack

Like other autoimmune diseases, type 1 diabetes occurs when a person's immune system mistakenly attacks itself rather than foreign cells. In autoimmune-type diabetes, the insulin-producing cells in the pancreas are under attack. Over time, insulin production stops completely, and daily injections of the blood sugar-regulating hormone are needed.

GAD, or glutamine decarboxylase, is an important target of insulin-producing cells for the immune system attack that leads to type 1 diabetes and to LADA .

In the study, researchers identified the specific response associated with the experimental drug's action. Those who showed the most improvement in insulin secretion also had increased production of the cells specifically known as CD4+ CD25+ cells. These cells suppress the immune attack on cells that make insulin.

"The study shows that it is possible to inhibit the autoimmune attack on the cells that make insulin, thereby slowing the progression of the disease," Essen-Moller says.

Blood Test Could Target Treatment

The treatment is based on animal studies done at UCLA in the 1990s. Daniel Kaufman, PhD, and colleagues showed treating diabetes-prone mice with the GAD protein prevented them from developing the disease. The also showed they could slow disease progression in mice who were on their way to developing type 1 diabetes."GAD suppresses the immune responses that cause the destruction of insulin-producing cells," Kaufman tells WebMD.

If these trials prove promising, Kaufman says the hope is that, like in the animal studies, the GAD protein-based drug will be shown to prevent type 1 diabetes among people at high risk.

Kaufman and UCLA colleague Allan Tobin, PhD, have developed a diagnostic blood test that can measure GAD protein antibodies and could easily identify people who could benefit from this treatment, he says.

SOURCES: International Diabetes Society annual meeting, March 29, 2004, Cambridge, England. Daniel Kaufman, PhD, professor, UCLA department of molecular and medical pharmacology. Anders Essen-Moller, president, Diamyd Medical, Stockholm, Sweden. Robert Goldstein, chief scientific officer, American Juvenile Diabetes Foundation.