Thursday, April 24, 2014
Los Angeles Times
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 say.
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 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.
The team selected 80 volunteers ages 18 to 40 who had been diagnosed with Type 1 diabetes within the last five years. Two-thirds of the 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.
The experimental and placebo groups also received insulin replacement therapy. All subjects were monitored for up to two years after the initial treatment.
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.
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.