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Gene chips generate therapeutic targets for multiple sclerosis
  

 

Scientists have used gene chips to compare different types of brain lesions from patients with multiple sclerosis (MS). They identified dozens of genes whose expression changed significantly between the lesions and tested two of the genes as potential therapeutic targets in mice. By manipulating these two genes, the researchers alleviated some symptoms of the disease in mice with a rodent form of MS.


a) Chronic active MS lesion shows a well-demarcated edge and a fibrotic, demyelinated center. b) Recent inflammation around the edge of the lesion in (a).

Lawrence Steinman and Renu Heller, both of Stanford University, California, led the research. From the beginning, their strategy was to use a step-by-step approach that involved microarrays, an animal model, and ultimately a clinical trial in human patients to evaluate novel therapies.

"This is the first description supporting molecular differences in the two types of lesions, and provides data that could ultimately influence the choice of treatment for acute versus chronic stages of the disease," write Stephen Tompkins and Stephen Miller of Northwestern University Medical School in Chicago in a News and Views piece that accompanies the study in Nature Medicine.

The scientists analyzed acute and chronic lesions from four MS patients at different stages of the disease. They found 39 genes with increased expression and 49 genes with decreased expression. They also identified several genes not previously known to be important in MS, including the two genes that became targets for therapy in mice.

Multiple sclerosis is a life-long chronic disease that attacks the central nervous system. The disease occurs when the body's white blood cells attack the myelin sheath insulating the brain and spinal cord. Multiple sclerosis is twice as common in women as it is in men, and the cause of the disease is unknown.

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Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8, 500-508 (May 2002).
 
Tompkins, S.M. & Miller, S.D. An array of possibilities for multiple sclerosis. Nat Med 8, 451-453 (May 2002).
 

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