Diabetes Vaccine Research

Thursday, 30 October 2008 16:14

Type 1 Diabetes
Diabetes is a condition that affects the body’s ability to use glucose, a form
of sugar derived from foods, for energy. Normally, the pancreas produces
insulin, a hormone, to allow glucose to enter the cells and be used as fuel.
People with type 1 diabetes don’t make insulin. The other kind, type 2
diabetes, occurs when the body can’t make effective use of insulin or doesn’t
make enough of it. In either case, despite having high levels of glucose
circulating in the blood, the cells are starved for energy. While people with
type 2 diabetes can often manage their disease with diet, lifestyle changes and
medication, those with type 1 need regular injections of insulin to stay
alive.

The American Diabetes Association estimates about 23.6 million Americans have
diabetes. About one million children and teens have type 1. It's usually
diagnosed during childhood. The Juvenile Diabetes Research Foundation estimates
15,000 children are diagnosed with the disease each year in the U.S.

An Immune System Gone Haywire
Type 1 diabetes occurs when the immune system mistakenly identifies the insulin
producing cells in the pancreas (called beta cells) as an enemy and mounts an
attack to destroy the cells. The exact reason for this inappropriate response
isn’t known. However, researchers believe some environmental trigger (like a
virus, perhaps) causes the beta cells to become inflamed. The normal response
to any kind of inflammation is to send a specific group of immune cells, called
immature dendritic cells, to the area. The dendritic cells are like patrols.
They seek out and identify the cause of the problem (normally a bacteria,
virus, etc.) and identify specific proteins on the invader. In the case of type
1 diabetes, the dendritic cells identify the inflamed beta cells as the source
of the problem. After contact with the chemical proteins (called antigens) on
the inflamed beta cells, the dendritic cells mature and travel back to the
lymph nodes. Here, the dendritic cells pass on the antigen information to
killer T-cells, the aggressive immune cells that form the attack squad. Armed
with the identification, the T-cells travel through the body, seeking out and
destroying any cell carrying the target protein. In the case of type 1
diabetes, the process leads to chronic inflammation of the beta cells and
eventually causes destruction of the cells.

Loss of insulin production is not an overnight process. Initially, many of the
beta cells are injured and unable to respond to glucose levels and produce
enough insulin. But some functioning beta cells remain. Generally, symptoms of
type 1 diabetes occur when 80 to 95 percent of beta cells are destroyed.

Vaccine Prevention
Researchers at the Children's Hospital of Pittsburgh of the University of
Pittsburgh Medical Center (UPMC) are trying to find a way to short-circuit the
body’s immune response in type 1 diabetes and prevent beta cell destruction.
Specifically, the investigators are targeting dendritic cells, by producing a
vaccine that prevents those cells from destroying the beta cells.

Each vaccine is personally made. To obtain enough dendritic cells, the patient
must undergo apheresis. Blood is collected through an intravenous tube and
passed through a machine, where the dendritic cells are separated from the
blood. Then, the remaining blood components are infused back into the body.
After two to four hours, doctors can collect as many as 20 million dendritic
cells.

Next, the dendritic cells are combined with antisense oligomucleotide (composed
of short pieces of genetic information). The antisense reprograms the
dendritic cells, hopefully deactivating the attack on the beta cells.

Some of the altered dendritic cells are injected into the patient’s abdomen in
an area near the pancreas. If all goes well, the new cells will take over the
function of the body’s natural dendritic cells, and redirect the attacking
T-cells away from the pancreas.

In one ongoing study, investigators gave the dendritic cell vaccine to mice in
the form of six injections over several weeks. So far, the study showed the
treatment halted the destructive T-cell actions and allowed the beta cells to
regenerate and begin producing insulin again. In fact, Diabetes Researcher,
Massimo Trucco, M.D., says all the mice were cured of their diabetes symptoms.

Trucco cautions that the treatment only restored about 20 percent of beta cell
production. In humans, that may be enough reserve function to allow patients to
live without insulin injections as long as they maintain a healthy diet and
lifestyle. However, if a patient strays outside the healthy limits, the body
may not be able to produce enough insulin and an injection may still be needed.

Currently, researchers are testing the dendritic cell vaccine for type 1
diabetes in human clinical trials. 15 volunteers will receive the vaccine. The
goal is to study the safety of the vaccine rather than its effectiveness.
Eventually, Trucco hopes to be able to intervene early in the process of beta
cell destruction so that patients can maintain more insulin-producing
capability.

AUDIENCE INQUIRY

For information about the trial, log onto www.clinicaltrials.gov.
Then type the trial ID number in the search box: NCT00445913.

For general information about diabetes:
American Diabetes Association,http://www.diabetes.org
Juvenile Diabetes Research Foundation, http://www.jdrf.org
National Institute of Diabetes and Digestive and Kidney Diseases,
http://www.niddk.nih.gov

The Kentucky Diabetes Prevention and Control Program (KDPCP)
chfs.ky.gov/dph/ach/cd/diabetes.htm

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