'Reverse vaccine' may treat early diabetes

2013-06-30T00:00:00Z 'Reverse vaccine' may treat early diabetesBrad Balukjian Los Angeles Times Arizona Daily Star
June 30, 2013 12:00 am  • 

LOS ANGELES - A "reverse vaccine" that allows people with Type 1 diabetes to produce their own insulin has passed its first test with human subjects, according to a new study. The success points to a potential new strategy for treating those in the early stages of the disease, experts said.

The therapy is designed to protect cells in the pancreas that make insulin, a hormone the body needs to convert sugars and starches into energy. In people with Type 1 diabetes, the immune system goes haywire and attacks those crucial insulin-producing cells for reasons that medical researchers don't understand.

Researchers dubbed the treatment a reverse vaccine because it suppresses the immune system instead of stimulating it. As hoped, the experimental vaccine reduced the number of immune system "killer" cells that went on the attack.

"We're trying to turn off one specific immune response," said Dr. Lawrence Steinman, a Stanford immunologist and senior author of the study published Wednesday in Science Translational Medicine.

About 1.25 million Americans have Type 1 diabetes. For nearly 100 years, the standard treatment has been insulin replacement therapy in which insulin is injected in amounts that correspond with blood sugar levels.

Attempts at new treatments and cures focused on suppressing large portions of the immune system - sometimes using powerful drugs developed for other conditions, such as the blood cancer lymphoma. Steinman called this the "big hammer" approach.

"We're trying to do something different," he said. "We want to eliminate just the immune cells that attack the insulin-producing cells in the pancreas."

Steinman and his team designed a molecule that contained the gene for making proinsulin, the precursor to insulin. The molecule also included instructions for triggering the killer cells' response and then shutting it down.

If everything went as planned, the DNA molecule would suppress the killer cells and allow the pancreatic cells to function properly, producing insulin.

After successful trials with diabetic mice, the team prepared to test its vaccine on humans. They selected 80 volunteers ages 18 to 40 who had been diagnosed with Type 1 diabetes within the last five years. After that time, many Type 1 sufferers have already lost all of their insulin-producing cells, Steinman said. (Although many people with Type 1 diabetes are diagnosed as children, the researches avoided testing their reverse vaccine on kids because of safety concerns.)

Two-thirds of the study volunteers received the reverse vaccine in one of four doses ranging from 0.3 to 6.0 milligrams. The rest of the volunteers got a placebo. Injections were made once a week for 12 weeks.

Throughout the study, the experimental and placebo groups also received insulin replacement therapy. All subjects were monitored for up to two years after the initial treatment to watch for any side effects.

To see whether the vaccine was working, the team measured two key components of the volunteers' blood: killer cells and C-peptide, a protein involved with making insulin.

Compared with patients who got the placebo, those who received the vaccine in 1.0 and 3.0 mg doses saw beneficial improvements in their levels of C-peptide.

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