http://www.sciencedaily.com/releases/2001/12/011221080824.htm
Source: University Of
Wisconsin-Madison (http://www.wisc.edu/)
MADISON - A common antibiotic, long
used to treat infections in humans, may have potential as a treatment for
multiple sclerosis, a devastating disease of the central nervous system,
according to a new study published today, Dec. 21, in the Annals of Neurology.
The drug, minocycline, is a member
of the tetracycline family of antibiotics and was tested in a condition
that mimics MS. Study results portray a potential treatment for MS that
could significantly decrease the severity of disease attacks or even block
the onset of relapses, hence ameliorating many of the disease's debilitating
symptoms.
The drug was tested in rats with
autoimmune encephalomyelitis. "Animals treated with minocycline did not
develop neurologic dysfunction or had a less severe course than untreated
rats," says Ian D. Duncan, a University of Wisconsin-Madison neurology
professor in the Department of Medical Sciences in the School of Veterinary
Medicine and the senior author of the study performed in collaboration
with C. Linington of the Max Planck Institute of Neurobiology in Germany.
"This clinical difference was confirmed
by the relative lack of pathologic change in the nervous system of treated
animals," Duncan says. "We therefore think that a similar therapy could
be used in MS patients with early relapsing-remitting disease."
In many respects, MS remains an enigma
to medical science. The majority of patients have a relapsing-remitting
course of disease with later more chronic progression in many cases. While
the trigger for relapses is often unclear, infectious disease such as a
cold or flu are frequently associated with their onset. There is no known
cause or cure and treatments to date have proved to be only partially effective.
The disease is especially common in far northern and southern latitudes;
the farther from the equator, the greater the prevalence of the disease.
The disease is characterized by inflammation
and loss of the myelin sheaths that insulate nerve fibers of the central
nervous system. Eventually there is scarring and nerve fiber loss. The
location of the inflammation in the central nervous system - the brain
and spinal cord - varies from patient to patient and from episode to episode.
"In the rat model, we show that you
can treat the animal successfully either before or after the onset of the
disease," Duncan says. In other words, in the context of the human disease
the drug could be given when patients start to show signs of neurologic
illness to forestall MS's progressive, nerve-damaging inflammatory episodes,
or prior to a potential relapse.
"We believe," notes Duncan, "that
the drug is acting at many levels. While it has effects on the peripheral
immune response, its actions may be primarily as an anti-inflammatory compound.
Indeed, the drug is widely used in another autoimmune disease, rheumatoid
arthritis, where it is thought to play such a role."
In the rat model Duncan and his colleagues
used, they believe that minocycline primarily inhibits the inflammatory
cascade in the central nervous system, particularly the activation of a
cell known as a microglial cell, a step that may be critical to the loss
of myelin and the myelin-producing cells. Duncan says evidence from other
labs has shown that minocycline can protect the nerve cell or fiber itself
from loss in other disorders; this may be additionally useful in MS.
"If we are correct that it is targeting
microglial cells, then this raises the possibility that the drug or compounds
with similar actions could be used in other neurologic diseases such as
Alzheimer's or Parkinson's disease where microglial activation may be the
common final pathway in neuron loss," says Duncan. "This will require further
work, however."
The drug will be tested in humans
next year in a Phase I clinical trial in MS patients at the University
of Calgary. "It is very important that a well-conducted clinical trial
is carried out to test whether it is safe and has efficacy in MS," says
Duncan. "As envisaged, minocycline could have advantages over other drugs
presently used, notably the interferons or copolymer I, as it is less expensive,
could be administered orally, and only for prescribed periods at the time
of ongoing disease."
Co-authors of the paper published
today include Natalija Popovic, Brian Goetz, Su-Chun Zhang, all of the
UW-Madison School of Veterinary Medicine; and Anna Schubart and Linington
of the Max Planck Institute for Neurobiology, Martinsried, Germany.
This story has been adapted from
a news release issued by University Of Wisconsin-Madison for journalists
and other members of the public. If you wish to quote from any part of
this story, please credit University Of Wisconsin-Madison as the original
source. You may also wish to include the following link in any citation:
http://www.sciencedaily.com/releases/2001/12/011221080824.htm
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Date: Posted 12/21/2001
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