Old Drug, New Use: New Research Shows
Common Cholesterol-Lowering Drug Reduces
Multiple Sclerosis Symptoms in Mice
For release: Monday, January 06, 2003
A new study shows that a widely prescribed
cholesterol-lowering drug dramatically
reduces symptoms of multiple sclerosis
(MS) in mice. Results of the study suggest
that statins, which are commonly used to
prevent heart attack and stroke, could be
a possible new treatment for MS and other
autoimmune disorders. The study was funded
in part by the National Institute of
Neurological Disorders and Stroke (NINDS)
and appears in the November 7, 2002, issue
of Nature 1
.
"These are very provocative results,
because we've shown that statins can
regulate the immune system response in an
animal model for multiple sclerosis," says
Scott Zamvil, M.D., Ph.D., assistant
professor of neurology at the University
of California at San Francisco and senior
author of the study.
In the study, a daily dose of atorvastatin
(brand name Lipitor), given for several
weeks, reduced inflammation in the central
nervous system and reversed some emerging
paralysis in mice with a disease closely
resembling MS, a disabling immune disorder
affecting about 2.5 million people
worldwide.
If the drug proves effective in human
trials, statins, which can be taken in
pill form, would offer an attractive
alternative or complement to existing
therapies for MS. Currently approved
treatments are given by injection, often
have serious side effects, and are only
partly effective, Dr. Zamvil says.
"We don't know if or how well statins
would work in reducing symptoms of MS in
humans, but we do know that they are well
tolerated when given orally," says Dr.
Zamvil. Still, there are some risks.
Statins can cause liver damage in a small
percent of patients, and they carry a
small risk of serious muscle damage.
Scientists believe MS develops when the
body's immune cells led by so-called
helper T cells attack myelin, the fatty
insulating sheath surrounding nerve cells.
The damage to myelin and the underlying
neurons in both the brain and spinal cord
leads to impaired cell communication and
progressive physical disability.
MS symptoms include fatigue, vision
problems, numbness, impaired balance, and
paralysis. There are currently no
treatments that can stop the disease,
although a few treatments do slow its
progression.
Atorvastatin appears to help the body
produce protective molecules that fight
inflammation and inhibit the production of
toxic molecules, the researchers say.
Previous studies in test tubes have also
shown neuroprotective effects, suggesting
that the drug might be used to treat such
neurodegenerative diseases as Alzheimer's.
"In the very near future we may have a
variety of new uses for statins," Dr.
Zamvil says.
Because statins have a different mechanism
of action than current treatments, they
may be able to work in tandem with other
MS treatments. Since MS is a multi-stage
disease, statins might be used along with
approved treatments -- copaxone or beta
interferons -- to treat the early,
inflammatory stage of the disease and
possibly to delay later stages, Dr. Zamvil
says. Another drug, novantrone, is
approved to treat symptoms related to
later-stage neuron loss, he says.
The mouse findings support the results of
a test-tube study of human blood samples
published in the October 8, 2002, issue of
Neurology 2
, which compared the effectiveness of
three statin drugs to interferon beta
proteins at reducing inflammation in human
tissue samples. Dr. Zamvil says that
because the two studies use different
methods they are difficult to compare, but
they both clearly show an
anti-inflammatory effect of statins.
"Our study is a new stimulus for examining
how statins might help patients in the
early stages of MS and many other
autoimmune diseases," says Dr. Zamvil.
"But we'll have to wait for clinical trial
results to see whether we can apply what
we've learned to patients."
The researchers say their next step is to
test the effectiveness of atorvastatin in
patients with early stage MS.
1
Youssef S, Stuve O, Patarroyo JC, Ruiz PJ,
Radosevich JL, Hur EM, Bravo M, Mitchell
DJ, Sobel RA, Steinman L, Zamvil SS. "The
HMG-CoA reductase inhibitor, atorvastatin,
promotes a Th2 bias and reverses paralysis
in central nervous system autoimmune
disease." Nature, November 7,
2002; vol. 420, pp. 78-84.
2
Neuhaus O, Strasser-Fuchs S, Fazekas F,
Kieseier BC, Niederweiser G, Hartung HP,
Archelos JJ. "Statins as immunomodulators:
Comparison with interferon-Beta1b in MS."
Neurology, October 8, 2002; vol.
59, pp. 990-997.
- By Tania Zeigler
Date Last Modified: Tuesday, January
24, 2006
