Now
specific conditions in mice with
the MS-like disorder EAE,
or experimental autoimmune
encephalitis. They were trying to
figure out whether manipulating
these two genes would affect EAE.
“It was like the disease process
sat up and talked to us,” says
Dr. Ransohoff. “The genes were
more active when the mice got
sick, and less active when the
disease improved. Through some
difficult laboratory techniques,
we found that these genes were
instructing the chemokine
proteins.” Furthermore, Dr.
Ransohoff’s team discovered
that the chemokines, in turn,
attracted immune cells to the
brain in mice with EAE, resulting
in disease activity (The FASEB
Journal 1993;7:592–600). This
important new finding would
influence our understanding
of MS and pave the way for
potential new treatments.
For this and other pioneering
work, Dr. Ransohoff was chosen
by a committee of peers to
receive the 2012 John Dystel
Prize for Multiple Sclerosis
Research. (See “About the John
Dystel Prize,” p. 59.) The prize
was presented at the annual
meeting of the American
Academy of Neurology in New
Orleans in April.
The ’neuro guy’
Dr. Ransohoff considers
himself lucky to have “tripped
over” this discovery, which
introduced him to the relatively
new field of chemokine study.
“I got completely hooked!”
says Dr. Ransohoff. “I was the
only person at the chemokine
meetings who was interested
in their role in the nervous
system, so I became known as
‘the neuro guy.’ ”
Dr. Ransohoff’s team
then began to investigate
chemokines in immune cells
isolated from people with
MS. “Chemokines function
similarly in humans and mice,
unlike some other proteins in
the immune system, so it was
these proteins in total,” says Dr.
Ransohoff. “You can mix and
match them, but you always need
one of each—one selectin, one
integrin and one chemokine, and
each one’s receptor—for immune
cells to go into the brain.” In fact,
Tysabri, a current MS therapy,
works by preventing one type of
integrin from docking onto its
receptor.
MS treatment possibilities
Now it looks as if keeping
chemokines from docking onto
“It was like the disease
process sat up and talked
to us.”
natural to go from studying
EAE to MS,” he says.
His results showed that blood
levels of specific chemokines
were, in fact, altered during MS
attacks. He also discovered that
the receptors for chemokines—
the docking sites where these
proteins attach, in much the
same way as a lock accepts a
specific key—were present on
numerous cells involved in the
immune response (The Journal
of Clinical Investigation
1999;103:807–815).
It’s now known that
chemokines and other proteins,
called selectins and integrins,
actually enable immune cells
to enter the brain from the
bloodstream in people with MS.
“There are about 100 types of
their receptors might prove to
be a more specific treatment
strategy than working with
integrins, because integrins
affect the immune system more
broadly than do chemokines.
It’s possible that this wide-
ranging effect is why people
taking Tysabri are more at risk
for the brain infection known
as progressive multifocal
leukoencephalopathy (PML).
