Contents - Winter 2008

Potential New Weapon in Fight Against Inflammatory Disease

By Noelle Chorney

Inflammatory disease often causes chronic pain and debilitation. At worst, it can cause death.

John Gordon. Photo courtesy Debra Marshall.

A new drug developed by University of Saskatchewan immunologist John Gordon, however, promises improved treatment for inflammatory illnesses. These include arthritis and inflammatory bowel disease, as well as inflammation associated with life-threatening conditions such as cystic fibrosis and complications caused by heart attack and stroke.

“If G31P performs the way we think it will, the effects on human health will be remarkable,” Gordon says.

The protein G31P, for which the U of S owns the patent, shows excellent potential to target inflammatory responses more specifically than current corticosteroid treatment does, he says, noting corticosteroids stop inflammation but also cause several unwanted and potentially serious side effects.

G31P targets only proteins that activate a specific group of white blood cells known as neutrophils. Other immune system cells are able to continue responses that are safe and necessary to the patient’s health, while the ones that cause dangerous inflammation are controlled.

He notes the importance of blocking the activation of neutrophils with G31P. “Neutrophils are the primary cause of inflammation damage in a large number of cases,” Gordon says.

Animal testing has shown G31P to be effective in treating bacterial lung infections.

Further development of the drug, including clinical trials on humans, will take place in partnership with Pacgen Biopharmaceuticals Corporation, based in Vancouver. A grant from the Canadian Institutes of Health Research will aid in determining which ailments would be best to take to clinical trials.

One likely candidate is known as ischemia-reperfusion injury, a condition that occurs when toxins build up in cells cut off from blood supply. When the blood returns, those toxins rush into the blood system, causing inflammation. This complication is commonly related to organ transplants, heart attacks and strokes.

Aspiration pneumonia, in which stomach contents are regurgitated into the lungs during surgery, drug overdose or head trauma, is another potential candidate. Roughly 30 per cent of patients die from complications related to the condition.

Successful trials and introduction of the new drug could offer benefits to patients within the next five years, says Gordon.

Treating Asthma Patients with Their Own Cells

In animal experiments, Dr. John Gordon and colleagues have been able to eliminate asthma using a new therapy they’ve developed. They have also proven that the treatment works with human cells from allergic subjects.

“Our research shows great promise for asthmatics,” says Gordon. “Current asthma drugs only treat symptoms—they don’t go after the cause. Our treatment has the potential to get at the root of what causes asthma.”

Gordon’s research focuses on dendritic cells, which act as “on/off” switches for the immune system. In asthmatic individuals, dendritic cells capture inhaled allergens and present them to T cells within the immune system, says Gordon.

“The T cells then switch into an allergic, or attack mode,” he says. “That form of attack appears as asthma.”

The new treatment involves withdrawing blood from an asthmatic animal, then purifying out dendritic cells. The cells are maintained in the lab for a period of time in the presence of a protein that tells them to switch off the allergic reaction. Those cells are then injected back into the animal, where they pass on the “off” message to allergic T cells and other dendritic cells.

After one treatment on asthmatic animals, the researchers recorded a 60 to 70 per cent decrease in asthma symptoms. After two treatments, they recorded a 90 to 95 per cent decrease in all animals tested.

Using human dendritic cells, the research team has demonstrated in the lab that they can create allergic T cell-targeting dendritic cells, which turn off the allergic reaction. The next step is to inject the cells back into the asthmatic subjects to prove that the treatment works on humans.

While allergen therapy shows obvious promise in the pursuit of a cure for asthma, it is also being tested as a treatment for multiple sclerosis, arthritis and other autoimmune diseases.