Autoimmune disease – retraining white blood cells

How can the immune system be reprogrammed once it starts to attack its own body? EPFL scientists retrained white blood cells responsible for type I diabetes, a common autoimmune disease. Using a modified protein, they precisely targeted these white blood cells (T-lymphocytes, or T-cells) that were attacking pancreatic cells and causing the disease. When tested on laboratory mice, the therapy eliminated all signs of the pathology. This same method could be extremely promising in treating multiple sclerosis as well. The scientists have just launched a start-up Anokion SA on the Lausanne campus, and are planning to conduct clinical trials within the next two years. Their discovery has been published in the journal PNAS (Proceedings of the National Academy of Science).

To retrain the rebellious white blood cells, the researchers began with a relatively simple observation. Every day, thousands of our cells die. Each time a cell expires, it sends out a message to the immune system. If the death is caused by trauma, such as inflammation, the message tends to stimulate white blood cells to become aggressive. But if the cell dies a programmed death at the end of its natural life cycle, it sends out a calming signal.

In the human body there is a type of cell that dies off profusely, at the order of 200 billion per day: red blood cells. There are as many calming signals transmitted daily to the immune system.

The scientists therefore attached the pancreatic protein targeted by T-cells in type I diabetes to red blood cells. “Our idea was that by associating the protein under attack to a soothing event, like the programmed death of red blood cells, we would reduce the intensity of the immune response,” explains Jeffrey Hubbell, co-author of the study. To do this, the researchers opted for state-of-the-art bioengineering: the protein, equipped, with a hook of molecular size, is able to attach itself to red blood cells. Billions of these were manufactured and then simply injected into the body.

Eradication of diabetes symptoms
As these billions of red blood cells died their programmed death, they released two signals: the artificially attached pancreatic protein, and the soothing signal. The association of these two elements retrained the T lymphocytes to stop attacking the pancreatic cells - like Pavlov’s dog who associates the ringing of a bell with a good or bad omen. “It was a total success. We were able to completely eliminate the immune response in type I diabetes in mice,” explains Hubbell.

Minimizing risks and side effects
Co-author Stephan Kontos adds that the great advantage of this approach is its extreme precision. “Our method carries very little risk and should not introduce significant side effects, in the sense that we are not targeting the entire immune system, but just the specific kind of T-cells involved in the disease.”

The scientists are planning to conduct clinical trials in 2014 at the earliest. Instead of directly testing the treatment on disease, their initial tests will aim to counteract the undesired immune response to a drug known for its effectiveness against gout. “We chose to begin with this application before we tackled diabetes or multiple sclerosis, since we know that we can control and understand all of the parameters,” explains Hubbell.

Currently, the researchers are also testing the potential of this method in treating multiple sclerosis. In this disease, T-cells destroy myelin cells which form a protective sheath around nerve fibers. They are also studying the potential of their method with another kind of white blood cell, B-lymphocytes, involved in many other autoimmune diseases.