DiaPep277 blocks the immune system’s destruction of pancreatic beta cells in humans.Scientists at the Weizmann Institute in Rehovot, Israel, have developed the first successful vaccine for Type I diabetes. The vaccine blocks the immune system’s destruction of pancreatic beta cells in humans.

The drug, DiaPep277, offers the possibility both of preventing the onset of the disease in those with a genetic risk and of halting its progression in those whose cells have already begun to die.

With Phase II trials on DiaPep277 successfully completed, Phase III trials are to begin in various centers around the world next year. Peptor Ltd. – the Rehovot biopharmaceutical company that purchased the rights – is planning to present an application to the U.S. Food and Drug Administration in 2004.

A team of researchers, led by Weizmann’s Irun Cohen, has worked more than 10 years on a small peptide fragment known as p277, despite skepticism among others in the field about its possible efficacy.

Results on a mouse model were dramatic, and the team proceeded to show its efficacy on patients, 200 of whom have been treated successfully in Israel and in England, Hungary, Bulgaria and Germany. Based on the results of their research, Peptor developed DiaPep277.

Cohen, Dana Elias (then a postdoctoral fellow at Weizmann and now vice president for research and development at Peptor), and colleagues reported on the clinical study performed at Hadassah-University Hospital in Jerusalem’s Ein Kerem by Itamar Raz, president of the Israel Diabetes Association and head of the hospital’s diabetes unit, in the British journal The Lancet.

The researchers proved three injections in six months of DiaPep277 were successful in arresting the progression of Type l diabetes in newly diagnosed patients – without displaying any harmful or significant side effects and without participants leaving the study.

Recent data show between 120 million and140 million people suffer from one of the two types of diabetes.

Type I (insulin-dependent) usually results from an autoimmune disorder in which the immune system mistakenly attacks the body’s insulin-producing pancreatic cells, reducing and ultimately stopping all insulin production. Sufferers need to test their blood sugar levels and inject insulin several times daily.

Type II is a metabolic disorder resulting from the body’s inability to properly use insulin. Patients with the more severe cases of Type II diabetes must supplement their natural insulin production with insulin injections.

The Phase II study was of 35 male patients 16-55 who were newly diagnosed with Type I. Eighteen received injections of DiaPep277 at the beginning of the study, at one month, and at six months; 17 received three injections of a placebo. Those who received DiaPep277 showed a halt or delay in the attack upon, or destruction of, their beta cells when examined at a follow-up 10 months after the first injection. These results were evident in the level of the body’s own insulin production and thus a decreased need for insulin injections. The researchers were able to trace the mechanism of this improvement to changes in the patients’ immune lymphocytes, called T-cells. Those receiving the placebo showed a significant decline in their natural insulin production and a persistent rise in the need for insulin injections.

“The older you are, the slower the progression of beta-cell destruction,” Cohen said.

In children, the destruction of pancreatic cells is very rapid, taking place even in a few months, Raz said. People at genetic risk for the disease who are exposed to a specific virus, toxic material, or food are likely to develop Type I diabetes. Phase II trials on children seven to 16 showed an improvement, but it was not statistically significant.

Younger children are now being tested using this strategy, Elias said.

For the past several years, Cohen and his team have been studying the mechanism by which the immune system destroys the insulin-producing pancreatic cells. Working with mice, they discovered a particular protein is closely linked to this destructive process. It acts like an antigen, prompting the immune cells to attack. Further investigation revealed injecting diabetic mice with p277 – a small peptide fragment of the protein – shut down the immune response, preventing the progression of Type I diabetes.

The peptide essentially acts to “re-educate” the immune cells, switching off their destructive activity, Cohen said.

The idea for using p277 stemmed from the discovery the immune system has different options to choose from in responding to an antigen. It can act to destroy the antigen or protect it from destruction. In this case, it indirectly prevents the pancreatic cells from being destroyed.

About 15 agents have been found to halt destruction of beta cells in mice, but none of them worked in humans, Raz said.

“No one believed it would work in people,” he said.

Peptor, which was established in 1993, now has 51 employees in Israel and in Germany. It will soon start preliminary testing on two other peptides, including one for kidney damage due to diabetes.