2002-06-03 16:50:49 -0400
By Merritt McKinney
NEW YORK (Reuters Health) - Two related chemicals in the body may be involved in preventing the nerve damage caused by the degenerative neurological disease multiple sclerosis (MS), the results of two new studies suggest.
The findings could lead to therapies that battle MS in a different way than current drugs, researchers say.
In MS, the slow destruction of myelin--the thin, protective coating that insulates nerve fibers in the brain and spine--can lead to numbness, muscle weakness and stiffness, impaired vision and coordination problems.
A substance called ciliary neurotrophic factor (CNTF) is believed to promote the survival of myelin-producing cells called oligodendrocytes. To find out how CNTF affects myelin-destroying diseases such as MS, a team led by Dr. Ralf Gold, of the Julius-Maximilians-Universitat-Wurzburg in Germany, studied mice that lacked the gene for CNTF. They worked with mice that were prone to develop experimental autoimmune encephalomyelitis, or EAE, a condition that also destroys myelin and that is used by researchers to mimic MS in mice.
The CNTF-lacking mice and a group of mice that had the CNTF gene developed EAE, but the MS-like illness started earlier and was more severe in mice without CNTF, according to a report in the June issue of the journal Nature Medicine. The mice without CNTF experienced much more drastic destruction of oligodendrocytes.
The researchers suspect that CNTF helps prevent myelin from being destroyed by acting on a substance called tumor necrosis factor (TNF). When mice lacking CNTF were treated with an antiserum that blocks TNF, the severity of the disease was reduced.
CNTF may be just the tip of the iceberg, according to Gold. He told Reuters Health that a number of other chemicals like CNTF may also have an effect on the severity of MS. Eventually, it may be possible to combine some of these chemicals, known as cytokines, with current MS therapy, Gold pointed out.
In another article in the same issue, Dr. Trevor J. Kilpatrick of the University of Melbourne in Australia and associates report that a molecule related to CNTF reduces demyelination in mice with EAE.
"We have found that administration of the molecule leukemia inhibitory factor reduces the severity of demyelinating disease in a mouse model of multiple sclerosis," Kilpatrick told Reuters Health.
The significance of the finding, he said, is that leukemia inhibitory factor, or LIF, works by preventing cell death, particularly of oligodendrocytes, which are "specifically targeted in MS." He noted that all current MS therapies work by combating inflammation rather than by preventing cell death.
Kilpatrick and his colleagues also found that the activation of LIF is a normal part of the nervous system's response that limits the severity of an injury. This discovery fits in well with the work by Gold's team that showed that mice lacking CNTF, which Kilpatrick said is a "sister molecule" of LIF, increases the severity of an MS-like illness in mice.
"CNTF and LIF and the receptors that they activate may be key determinants of the severity of MS," Kilpatrick said.
Currently, there is no appropriate therapy to treat the nerve cell death in MS patients, according to the Australian scientist.
"LIF might, in principle, ultimately be attractive therapy in combination with standard anti-inflammatory treatments," he said.
SOURCE: Nature Medicine 2002;8:613-624.
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