Researchers at Stanford University, the University of Connecticut and other institutions report having uncovered hundreds of proteins that may be active at different stages of multiple sclerosis. They conducted high-tech analyses of different types and stages of MS brain lesions. To validate the approach, they narrowed in on two of the proteins and blocked their activity using existing drugs in mouse models of MS, and were able to improve symptoms. The study, appearing in the February 17, 2008 issue of Nature, was funded by the National MS Society and National Institutes of Health.
Details: The team focused in on lesions in brain specimens from six people who had had different forms of MS and compared them to non-disease specimens. In what was probably the most comprehensive biochemical profiling of MS lesions to date, they used high-tech proteomics and mass spectrometry to identify the presence of thousands of proteins within different types of lesions (also called plaques). The lesions were classified as 1) acute lesions with active inflammation, 2) chronic lesions with active inflammation and 3) chronic lesions with little or no inflammation.
Their first screen identified thousands of proteins present in the lesions. They then narrowed this list down to proteins that were unique to each stage of lesion, and found 158 proteins unique to the acute active lesions; 416 proteins unique to chronic active lesions; and 236 proteins unique to chronic, non-active lesions.
About half of the proteins unique to specific lesions were of unknown function. Those of known function related to many different aspects of cell structure and function. A few of the proteins unique to the chronic, active lesions related to blood coagulation. To help verify the usefulness of this screening strategy, the team narrowed in on two of the coagulation proteins (“tissue factor,” which promotes blood coagulation and inflammation, and “protein C inhibitor,” which blocks the anticoagulation activity of another protein, “protein C”) and tested the impact of blocking either protein with existing drugs given to mice with MS-like disease. Drugs that blocked either protein were able to improve symptoms of the disease in mice, but not stop relapses or alter disease course.
The authors comment that engineering drugs to specifically alter the inflammatory aspects of coagulant proteins may be a useful new approach to treating multiple sclerosis, avoiding risks of increasing bleeding that currently available anti-coagulant drugs hold.
“We need new approaches to get at the complex nature of MS,” commented John R. Richert, MD, executive vice president for research and clinical programs at the National MS Society. “This study confirms the promise of this high-tech approach, and has the potential to send us down whole new pathways of discovery,” he added.
These findings, based on the analysis of brain specimens, also confirm how important it is that researchers have MS tissues available to study the disease. The National MS Society is funding MS brain banks in Los Angeles, Englewood, Colorado, and a new one is coming online soon in Chicago. People with MS can make a real difference by arranging to donate their brain and spinal cord tissues when they die. Planning ahead is essential. Individuals interested in the possibility of tissue donation can contact these banks as follows:
Rocky Mountain MS Center
701 East Hampden Avenue , Suite 420
Englewood , CO 80110
Phone: (303) 788-4030
Web site: http://www.mscenter.org/
MS Human Neurospecimen Bank
Veteran Administration Medical Center
11301 Wilshire Boulevard
Los Angeles, CA 90073
Phone: (310) 268-3536
Phone: (310) 478-3711 after hours and weekends (Please ask for the Brain Bank)
Web site: www.loni.ucla.edu/uclabrainbank/