Findings may lead to new treatments for disease
Irvine, Calif., Nov. 19 — Sea anemones use venom to stun their prey, but one component of that venom halts-and may reverse-the paralysis seen in an experimental form of multiple sclerosis, according to a study by UC Irvine's College of Medicine and the University of Marseilles, France.
If the findings conducted on rats prove effective in humans, they could result in a new class of drug treatments for multiple sclerosis, one of the most common diseases of the nervous system, known for its devastating and progressive loss of sensation and function. The study appears in the Nov. 20 issue of the Proceedings of the National Academy of Sciences.
Christine Beeton and Heike Wulff, physiology and biophysics researchers, and their colleagues found that a component of venom called ShK from the Caribbean sea anemone Stichodactyla helianthus blocks ion channels located in white blood cells that had been activated to cause an experimental form of multiple sclerosis called EAE. By blocking the channels on these activated cells, ShK prevented the activated cells from attacking the nervous system and causing paralysis.
The white blood cells, also known as T cells, that were activated to cause experimental MS, contained unusually high numbers of a particular ion channel. Usually, such inappropriately activated cells are destroyed by the body's thymus gland, which regulates production of immune cells. But in many cases of multiple sclerosis, these disease-causing cells slip through and can attack nerve cells. Ion channels are found on the surface of cells and play crucial roles in communicating between cells and regulating cellular behavior.
"This experimental form of multiple sclerosis is caused by T cells with high numbers of unique ion channels that may trigger the T cells into attacking neurons and eventually cause paralysis and death," said Beeton. "Our experiments show that we can block these channels, and only these channels, and protect neurons from damage. If these findings hold after testing in other animals and people, they may result in an effective treatment for MS."
Multiple sclerosis is a debilitating disease in which T cells and other components of the immune system literally attack their own nervous system, resulting in tremors, burning, sensory deprivation, paralysis and eventually death. Immune cells cause the disease by stripping away a protective sheath called myelin that normally surrounds neurons and helps them transmit crucial nerve signals.
The disease can strike the young and elderly and can take years to develop. The National Multiple Sclerosis Society estimates that between 250,000 and 350,000 people in the United States suffer from multiple sclerosis. There is no known cure, though certain treatments can address symptoms and even slow the disease's course if detected early.
ShK blocked the ion channels and stopped the activated cells' destructive activity. By continuously blocking these T cell channels with ShK, the researchers found they could reverse the experimental disease, even after the initial onset of symptoms. In some rats that were showing signs of paralysis, their function was nearly fully restored.
ShK is the most potent inhibitor known for these channels on the activated T cells, but its short life span in the bloodstream reduces its effectiveness as a therapeutic drug.
"ShK may not last long enough to prevent or treat disease on a long-term basis," Wulff said. "But it appears to match the biochemical structure of the channel well enough to block it and change the T cells' responses. Our group is searching for chemically similar substances that last longer in the body."
"This research shows that we may be able to effectively treat the disease while preserving the immune system by targeting a specific cellular ion channel," Beeton said. "Still, researchers will have to find out what dose works best to treat MS, whether it can work on other illnesses and at what stage of a disease treatment should begin."
The researchers' work was supported by the National Multiple Sclerosis Society, the French Association pour la Recherche sur La Sclérose en Plaques, Fondation pour la Recherche Medicale and the U.S. National Institutes of Health.
Beeton's and Wulff's colleagues in
the study include Michael Cahalan and George Chandy at UCI, Jocelyne Barbaria,
Olivier Clot-Faybesse, Dominique Bernard and Evelyne Béraud of the
Faculté de Médecine, Marseilles, France, and Michael Pennington
of Bachem Bioscience, King of Prussia, Pa. Béraud's team at the
University of Marseilles induced the experimental form of MS in the rats.
Michael Pennington and his team at Bachem synthesized the ShK venom component
that was used in the study.
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