"There are essentially two death pathways in cells, one that takes signals from the outside of the cell and one from the inside," explained study senior author Harris Perlman, an associate professor of molecular microbiology and immunology at Saint Louis University, in St. Louis. Normal cells are given signals to die at certain points to make room for new cells.
Perlman and his colleagues knocked out one gene from each pathway in mice with lupus. "Lo and behold, these mice that have two death pathways knocked out developed massive lupus," he said. "They died at four to five months of age."
Individuals with lupus produce more immune cells that carry too many of the proteins that prevent death. The more immune system cells a patient had, the more severe the disease was.
The next step is to manipulate these genes, or the proteins they produce, to restore a natural life cycle to the cells.
"If you can somehow turn off these anti-death genes then you can restore the balance again," Perlman said. "We have dome preliminary work and seen some positive results. We're not trying to do gene therapy approach. We're going to try to look at protein levels and remove proteins from the equation by inactivating them."
Although it's not clear that this finding specifically will bring relief to some people suffering from lupus, it is emblematic of a new era in research.
"We have a smorgasbord of discovery," Buyon said. "The challenge to industry and clinical trialists is picking and choosing which target to go after, because it costs so much to bring a drug to market."
Visit the Lupus Research Institute for more on what's being done in this field.
SOURCES: Harris Perlman, Ph.D., associate professor, molecular microbiology and immunology, Saint Louis Univ
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