Dec. 21, 2001 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.
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