Antibiotic May Be A Potential Therapy For Multiple Sclerosis

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Antibiotic May Be A Potential Therapy For Multiple Sclerosis

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 ls 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, Goetz,

Su-Chun Zhang, all of the UW-Madison School of Veterinary Medicine; and

Schubart and Linington of the Max Planck Institute for Neurobiology,

sried, Germany.