Researchers at Stanford University are tackling Type 1 diabetes by thinking backward. They've been searching for a way to treat the autoimmune disease while keeping insulin-producing cells in the pancreas alive.
The scientists have come one step closer to a cure for so-called juvenile diabetes with their “reverse vaccine,” which shuts down parts of the immune system that attack these insulin-producing beta cells.
“It’s a significant first step in showing that you can get a specific reduction of the pathological cells and leave the rest of the immune system intact,” said Stanford researcher Dr. Lawrence Steinman.
Steinman asked the simple question that vexes all scientists who study autoimmune diseases, in which the body uses the immune system to attack its own cells by mistake: “Why can’t we specifically turn off the immune response?”
How Does It Work?
The reverse vaccine uses an engineered plasmid—a small, circular piece of DNA that is separate from chromosomal DNA. The plasmid expresses proinsulin, the precursor of the hormone insulin.
Steinman describes the molecular engineering as akin to a brake in a car. It switches off part of the immune system, rather than just replacing lost insulin, as in most current treatments for Type 1 diabetes.
“As we were increasing the amount of insulin-producing cells in a very sensitive measure of the immune system, we showed there was a reduction in the number of killer immune cells that actually destroyed the insulin-producing pancreatic cells,” Steinman explained. "[There was a] highly specific reduction in the cells that are at the very pathology of this disease.”
The reverse vaccine is an improvement over other proposed cures for Type 1 diabetes that involve immunosuppression, or a more general suppression of the immune response. These methods can’t efficiently single out specific cells without hobbling the rest of the immune system, which needs to perform at its best to help the body fight off infections.
“Over the years, these earlier attempts aimed at tearing down chunks of the immune system,” Steinman said. The new reverse vaccine is a more targeted approach.
The researchers studied 80 patients who had recently been diagnosed with Type 1 diabetes and who were randomly sorted into two groups. The patients received either the proinsulin-expressing engineered plasmid or a placebo treatment.
Those who received the plasmid treatment showed increased C-peptide levels, which Steinman explains are the primary measure of the amount of insulin-producing cells in the body. And, he added, “as you preserve C-peptide you significantly reduce the chance of those horrible things happening to you later on in life.”
Patients treated with the plasmid also showed a decrease in their levels of proinsulin-specific cytotoxic cells, which can destroy beta cells.
Now that this therapy has been used effectively for Type 1 diabetes, researchers see the same technology being applied to the treatment of other autoimmune diseases and their triggers in the future.