Trials of Type 1 Diabetes Vaccines Bring Mixed Results
TUESDAY June 28, 2011 -- A vaccine developed to prevent the progression of type 1 diabetes shows some promise, while another designed to alter insulin production fails, according to the results of two new studies.
The results of both studies were slated to be presented Tuesday at the American Diabetes Association annual meeting in San Diego.
Type 1 diabetes often appears early in life and is thought to be an immune system disorder involving the destruction of insulin-producing beta cells in the pancreas. About 5 percent of diabetic people have the type 1 form of the disease.
For the first vaccine study, a drug called DiaPep27 -- developed to prevent the destruction of beta cells -- was tested in newly diagnosed diabetics.
The study focused on a specific protein, called the "heat shock protein," produced in type 1 diabetes.
"When presented to the immune system, [this protein] causes the immune system to attack beta cells," lead researcher of the first study, Dr. Itamar Raz, professor of medicine and head of the Hadassah Diabetes Center in Jerusalem, explained in a Sunday afternoon press conference.
The researchers believe that the "heat shock" protein activates immune system cells called T cells, which then destroy beta cells. However, it is thought that one can change destructive T cells into protective T cells, the researchers said.
In their work, Raz's team tweaked "heat shock" proteins to see if they could be made to protect beta cells from being attacked by T cells. This approach had been shown to work with mice with a form of type 1 diabetes, Raz noted.
In the current phase 2 trial, 100 patients recently diagnosed with type 1 diabetes were given DiaPep277. The vaccine worked, protecting beta cells in the same way it did in mice, the researchers say.
"When you inject the drug into the patient you activate the T cells to become protective T cells instead of being . . . attacking [T cells]," Raz said. The vaccine increased the number of T cells secreting cytokines, chemicals that kept the beta cells from being destroyed in an immune attack.
In addition, the beta cells continued to make and release insulin for up to two years after diagnosis. These promising results could lead the way toward preventing type 1 diabetes, Raz said.
Raz noted that the drug does not appear to cause harm to humans. "Around 500 people have been exposed to the drug, and the drug is very safe," he said.
DiaPep277 is now being tested in a phase 3 trial, the researchers said.
Dr. Stuart Weinerman, chief of the division of endocrinology at North Shore-LIJ Health System in New Hyde Park, N.Y., called the DiaPep277 vaccine "a novel, interesting approach to managing type 1 diabetes."
However, there are questions about what happens when you change the functioning of T cells, he said. "Will changing T cell function have adverse affects?" he asked. "Whenever you deal with autoimmunity that's the first thing you ask about -- are you affecting the ability to fight infections?"
A second study, which looked at whether combining glutamic acid decarboxylase (GAD) plus aluminum hydroxide to create an antigen could prevent the loss of insulin production in patients newly diagnosed with type 1 diabetes.
Unfortunately, while this approach appeared beneficial in mice, it did not work in humans, the investigators found.
They tested the antigen in one group and compared it to two other groups, including one made up of "controls," or untreated subjects. However, beta cell function in all three groups declined at similar rates.
"Although promising in animal models, so far, in human studies it failed to show an effect," lead researcher Dr. Jay S. Skyler, professor of medicine, pediatrics and psychology at the University of Miami Miller School of Medicine, said during the press conference.
The results were due to be presented at the meeting and were also simultaneously published in the June 27 online edition of The Lancet.
Commenting on both vaccine studies at the press conference, Dr. Desmond Schatz, professor and associate chairman of pediatrics and medical director of the Diabetes Center at the University of Florida in Gainesville, said the studies are important to understand how type 1 diabetes could be prevented, cured or prevented from recurring.
"It is my belief that prevention is absolutely necessary for cure to take place," Schatz said.
"We may think about reversing the disease, ultimately with organ transplantation or stem cells. In addition to preventing rejection we've got to prevent the disease from coming back, so these studies are absolutely key to understanding the mechanism and the prevention of recurring autoimmunity," Schatz explained.
For more information on diabetes, visit the U.S. National Library of Medicine.
Posted: June 2011
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