In the first trial with human subjects, it reduced the number of immune system 'killer' cells that attack crucial insulin-producing cells, study shows.

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, an immunologist at Stanford University 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 have 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 researchers 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, both 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 during and after treatment. But three months after the treatment stopped, C-peptide levels declined, indicating the vaccine had worn off, the team wrote.

Patients in the vaccine group, no matter the dosage, saw the number of killer cells fall and the amount of proinsulin rise over 15 weeks without affecting the rest of their immune system cells. The changes were much more modest in patients who got the placebo.

No significant side effects or safety concerns arose during the study, the team reported.

Dr. Hertzel Gerstein, an endocrinologist at McMaster University in Ontario who treats Type 1 diabetes patients, called the research encouraging, and said he was looking forward to further studies with many more patients.

"It's a small study with preliminary findings," he said. "It could or could not translate into anything clinically relevant. But certainly this holds some promise."

Dr. Peter Butler, director of the Larry L. Hillblom Islet Research Center at UCLA, said a reverse vaccine was a promising approach, but he was concerned that the benefits lasted only a few weeks. It might be impractical to keep the killer cells at bay with such a narrowly targeted vaccine, he said.

Steinman said his team was planning further tests with longer treatment periods.

"This is only a first step," he said. "But there is potential for protecting people from the ravages of this disease in the long run."

The study was funded by Bayhill Therapeutics, a start-up founded by Steinman and three of the study's co-authors. The company, now known as Tolerion Inc., aims to bring the vaccine to market.