More MS news articles for January 2001

'Master switch' found that controls battle with disease

Toronto scientists say protein turns off immune system


A team of Toronto scientists has found the Holy Grail of the body's signalling system -- the switch that turns off hormones and proteins which trigger diseases like cancer, heart disease, diabetes and other auto-immune syndromes.

The discovery, which they say they made in a "Eureka!" moment, could provide the key to developing ways to stop the progression of those ailments as well as organ rejection in transplant patients, says lead author Dr. Josef Penninger.

The findings were reported Thursday in the scientific journal Nature.

Scientists the world over have been searching for years for the master switch, said Penninger, who took great satisfaction from the fact that he and his team discovered something that was under everyone's nose all along.

"It's the Holy Grail of the signalling system, to switch it off," he said in an interview Wednesday. "Everybody was looking for this molecule. And we had it in front of our eyes all the way.

"We were kind of looking out of our left eye and didn't see what was out of our right eye."

The research team is drawn from the Ontario Cancer Institute at Princess Margaret Hospital, Toronto General Hospital and the semi-private Amgen Institute, affiliated with the University of Toronto.

The team has been responsible for a string of discoveries over the last two years, including a protein that stops the growth of colon cancer tumours, and learning that a virus can cause some forms of heart disease.

Their latest revelation is that a protein called CD45 is the master switch for the immune system. It sends the ceasefire order once the body has vanquished a foe such as a virus.

"Although the attack signal is a good thing when the body is invaded by disease, you must have a way to call in the troops once the enemy has been defeated," Penninger said. "Otherwise the immune system ... goes after healthy cells and results in diseases such as diabetes, multiple sclerosis, heart disease and even cancer."

Scientists have thought for more than a decade that CD45 played a much more limited role, that it simply regulated the behaviour of a couple of types of cells that are part of the immune system.

"This just became absolute paradigm in the field and two years ago I would have also believed in it completely," said Penninger, who published papers supporting that view of CD45's role.

But almost by accident his team discovered that CD45 has a much broader role and is responsible for regulating how the body's cells manage functions such as the growth of red and white blood cells, the regulation of viral infections and heart disease.

They proved their theory in mice, finding that CD45 controlled the development of a virus that induces heart disease.