91av

WHILE a cure for multiple sclerosis remains elusive, silencing key messengers
of the immune system might halt and even reverse its debilitating symptoms.
Several groups are now developing drugs to do this after promising tests in
animals.

MS is a result of immune cells attacking the protective myelin sheath that
coats nerves in the brain and spinal cord, causing a variety of symptoms such as
numbness, weakness and paralysis. What triggers this autoimmune reaction still
isn’t known.

But studies have shown that the cerebrospinal fluid in MS sufferers often
contains abnormally high levels of certain chemical signals called chemokines.
These chemokines summon immune cells such as monocytes and T cells to the
central nervous system, where they attack the myelin.

Targeting chemokines, or the receptors that detect them, might slow down or
halt the attack on myelin, giving the nerve coating a chance to recover,
researchers realised. “When we block the influx of T cells we are giving the
central nervous system a breather —time to repair itself,” says Thomas
Lane of the University of California, Irvine.

His team has created antibodies that bind to a chemokine called CXCL10 and
inactivate it. Lane picked CXCL10 because previous studies showed that levels of
the chemokine in the central nervous system shoot up during acute flare-ups.
When his team injected CXCL10 antibodies into mice with a condition like MS,
they found it slowed demyelination and even appeared to allow myelin to
regrow.

Crippled mice were able to walk again, Lane says. However, the reversal of
symptoms was not complete and despite continued injections the effects lasted
only a few days. This is probably because the CXCL10 antibodies, which came from
rabbits, provoked an immune response that neutralised them
(see 91av, 6 October, p 18).
Lane’s group is now repeating the tests with a different version
of the antibody.

“In terms of treating the inflammation aspects, Lane’s work is as promising
as anything one can imagine,” says Richard Ransohoff, an expert in chemokines
and multiple sclerosis at the Lerner Research Institute in Cleveland, Ohio. But
the work must be confirmed by human trials, he says.

Other researchers are pursuing similar strategies to Lane. Universities and
companies are investigating seven chemokines and five different chemokine
receptors.

Berlex Laboratories of Richmond, California, for example, has already begun
human trials of a small molecule that blocks a receptor called CCR1. Drugs based
on small molecules would be more practical than large proteins such as
antibodies because they can usually be taken as pills and don’t provoke an
immune reaction.

But tinkering with chemokines must be done with care, cautions Ransohoff.
“These molecules provide necessary immune functions. Completely eliminating them
isn’t safe.”