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Researchers discover the off
switch for disease signals
TORONTO -- Jan. 18, 2001 -- The role of a
gene that acts as the off switch for several disease signals
including cancer, heart disease and autoimmune diseases has been
discovered for the first time. The finding reported in today's
issue of Nature paves the way for future research into
how to turn off the cellular signals that trigger various diseases.
The discovery could lead to more targeted
control of diseases such as cancer, diabetes and heart disease
by turning off the communications signals that order the immune
system to go on the offensive, according to senior author Dr.
Josef Penninger, an immunologist at Princess Margaret Hospital's
Ontario Cancer Institute.
"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 says. "Otherwise the immune system continues fighting
and, after it destroys the invader, it goes after healthy cells
and results in diseases such as diabetes, multiple sclerosis,
heart disease or even cancer.
Penniger and colleagues at Toronto General
Hospital and the Amgen Research Institute discovered the role
of a key protein called CD45. The protein is responsible for
regulating how the body's cells respond to developmental signals
and manage functions such as the growth of red and white blood
cells, the regulation of viral infections and heart disease.
"Our cells rely on the delicate balance
of communications signals to grow normally and produce blood
cells," says Penniger. "However, when a signal cannot
be stopped, the cells overgrow and we run into trouble. We have
discovered that it is CD45 that sends the `cease fire' signal
to cells. This is the Holy Grail of the body's cellular signaling
system."
CD45 has been extensively studied for over
a decade and it was widely accepted in the scientific community
that its function was well understood. Penninger says the most
exciting thing for him in this study was proving the field wrong.
In the current study, Penninger and colleagues
Drs. Takehiko Sasaki and Junko Irie-Sasaki, two post-doctoral
fellows, found that CD45 controlled the development of virus-induced
heart disease. Mice without CD45 did not develop heart disease.
And because CD45 stops the body's immune system from attacking
foreign invaders, the discovery also has potential for finding
effective ways to prevent the body's rejection of donated organs
or bone marrow in transplantation.
"For me, this is what makes science so
exciting," said Dr. Penninger. "This finding will affect
an entire paradigm shift in how science looks at cellular signaling.
This was definitely a Eureka moment, in which we discovered an
entirely new function of a gene science had assumed was all figured
out."
Co-author Dr. Peter Liu, a cardiologist at
Toronto General Hospital, says the discovery points to a new
approach to treating chronic diseases.
"Most of the drug treatments we use to
manage or treat diseases today work on the "on switch,"
which works very well for acute diseases," says Liu.
However, with an aging population, more and
more people are affected by chronic diseases such as diabetes,
arthritis, cancer, obesity and heart disease, all of which result
from growth or inflammation that is left "on" and cannot
be turned off.
"Because of this discovery, we can begin
developing drug treatments that may someday turn off many of
the chronic diseases that affect a very large population of our
society," says Liu.
The research team's next step is to find ways
to restore the function of missing or damaged CD45 in search
of a way to essentially shut down cell growth in cancer and autoimmune
diseases.
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