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[IP] Reprogramming the immune system


Reprogramming the immune system

Approach uses the bodys own cells to fight multiple sclerosis
In multiple sclerosis, immune-system cells called T cells attack and damage
the myelin sheath that protects nerve cells, or neurons.

By Charlene Laino

Jan. 23   Its like pouring gasoline on a fire to put it out. Yes, you read
correctly: thats the best way to describe a novel approach that shows
for treating multiple sclerosis using an extremely large dose of the very
substance that is causing the disease to begin with.

FOR THE first time, scientists have shown that the experimental approach
in non-human primates with multiple sclerosis. And theres every reason to
believe, they say, that the same tactic could help stomp out symptoms in
humans suffering not only from MS, but also from other autoimmune diseases,
such as rheumatoid arthritis and diabetes.
       The feat is the latest to grow out of a new molecular-level
understanding of autoimmune diseases, the umbrella term for some 40-plus
conditions in which the bodys immune system  its first line of defense
against foreign invaders  runs amok.
       Researchers have known for years that autoimmune diseases result when
malfunctioning immune system mistakenly recognizes certain cells in the body
as the enemy and launches an all-out attack. In multiple sclerosis, the
sheath  the protective covering that surrounds nerve cells in the brain and
spinal cord  is the target.
       More recently, experiment showed that specialized immune-system cells
called T-helper cells are the key players, the culprits that produce
substances that attack and damage the myelin sheath. The result is
for the millions of Americans with the disease: fatigue, dim or blurred
vision, disturbed speech, memory loss, muscle weakness, even paralysis. The
lucky ones merely suffer mild weakness for decades (though always wondering
if their condition will worsen); others steadily deteriorate from repeated
Meanwhile, scientists were gaining a better understanding of a well-honed
immune system  a system in which the same T cells that wreak havoc in MS are
gallant warriors. It became clear that like soldiers, T-helper cells sit
for invasion from a foreign invader, be it a flu bug, food-borne bacteria or
other pathogen. Then, as soon as they recognize the enemy, these T cells turn
into commanding officers of sorts and begin multiplying until an entire army
is set to fight.
       But like any potent weapon, you want to control how much is
says the National Institutes of Healths Dr. Michael Lenardo. If the cells
just kept multiplying ... youd have a surfeit of T cells, very potent
activators that can actually kill you  as happens in toxic shock syndrome.

       Fortunately, every cell has a built-in suicide mechanism. When there
are too many soldiers, they are programmed to self-destruct, he says. A
healthy immune system doesnt let your T cells grow uncontrolled and kill
       Several years ago, Lenardo, a researcher at the National Institute of
Allergy and Infectious Diseases laboratory of immunology, decided to put the
new knowledge about the immune system in general and MS in particular to a
test. Since MS is an autoimmune disease in which T-helper cells are activated
that shouldnt be, Lenardo reasoned that he could thwart the disease if he
could just activate T-helper cells built-in suicide mechanism.
       Working at first in the lab, Lenardo proved his point. As expected,
T-helper cells exposed to small amounts of the proteins making up the myelin
sheaths were stimulated to attack the sheaths.
       But, paradoxically, when these activated T-helper cells were exposed
large amounts of the same proteins, they died off. Instead of robust
proliferation, which is what we expected, we got self-destruction, says
Lenardo. We observed negative feedback.

         Next, Lenardo tried the experiments in mice, with very dramatic
results. Not only did the MS mice become healthy, but the disease-causing T
cells were actually eliminated, he says.

       In the latest test, nine male marmoset monkeys were injected with just
enough myelin proteins to stimulate their T cells to attack myelin sheaths,
inducing a disease very similar to MS in humans. Three monkeys then received
additional large doses of myelin proteins, three got moderate doses, and
received nothing.
       About three months later, all three of the untreated monkeys showed
symptoms of the disease. In contrast, none of the primates who got large
of myelin had symptoms. The moderate-dose group didnt fare as well, with two
showing symptoms, though less severe ones than their untreated counterparts.
The report appears in the February issue of the Journal of Immunology.
       Imaging scans of the animals brains further validated the
observations. Magnetic resonance images revealed severe damage to the myelin
sheaths in two of the untreated monkeys and one of the moderate-dose monkeys.
Minor damage did occur in the large-dose group, indicating the disease
had not been completely thwarted although it had been greatly suppressed,
Lenardo says.
       Theyve re-educated an immune system gone awry, says Dr. Patricia
OLooney, director of biomedical research at the National Multiple Sclerosis
Society in New York. This certainly holds great promise.
       One of the most exciting aspects of the new work is that it marshals
the bodys own, nontoxic resources to fight off the disease. Similar to
chemotherapy for cancer, current treatments for MS and other autoimmune
diseases are atom bombs of sorts, killing or suppressing everything in their
wake, good or bad.
       Conceptually, we have a very powerful new tool, Lenardo says. It
selectively homes in only on those cells causing the disease rather than
shutting down the entire immune system.
       There are even advantages over other immune-based approaches to
autoimmune diseases, he says. The others just paralyze T cells, but they
could wake back up. This actually gets rid of them.
       With human testing still on the horizon, its too early to say whether
Lenardos approach is best. But with one in 20 Americans victim of one
autoimmune disease or another, at enormous personal cost in pain and
and at monetary costs topping $100 billion each year, its certainly worth a
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