A bit of serendipity and a lot of dying worms led researchers to a discovery that could open new treatment doors for a dizzying array of deadly illnesses.
Studying tiny roundworms, researchers at OMRF, the University of British Columbia and the University of Pittsburgh School of Medicine have discovered a protein may play a key role in the cell and tissue death process known as necrosis. That process, long thought to be chaotic and irreversible, is associated with illnesses ranging from heart disease and stroke to Alzheimer’s.
The new findings, published in the scientific journal Cell, show that necrosis might, in fact, be controlled by a protein known as SRP-6. If researchers can harness SRP-6, the protein could hold the key to halting cell death in neurological illnesses like Alzheimer’s, Parkinson’s and Huntington’s and also to new treatment paths for cancer, heart disease and various bacterial illnesses.
Researchers made the discovery in studies of a microscopic worm called C. elegans. With a tiny, translucent body and only 959 cells, the worms are frequently used for medical research.
In the current study, using a complex process to isolate and then remove certain genes, OMRF’s Robert Barstead, Ph.D., and Gary Moulder generated genetically modified “knock-out” worms that lacked the SRP-6 protein. When a collaborator at the University of Pittsburgh was collecting specimens of the worms—by chance using water instead of the more commonly used saline—he noticed that the genetically modified worms were dying in droves, while their normal counterparts remained healthy.
After additional investigation, the scientists determined that necrosis spurred by shock from the water was killing the worms that lacked the SRP-6 protein. The normal worms survived because the protein protected their cells.
“This discovery could translate into treatments for human disease,” said Barstead, who holds the G.T. Blankenship Chair in Alzheimer’s and Aging Research at OMRF.
Armed with the knowledge that SRP-6 protects against cell death, physicians could manipulate the levels in patients with certain diseases. For example, physicians could boost levels of the protein in patients suffering from neurological or cardiovascular disease to halt the process of necrosis. Conversely, in cancer patients, doctors could deprive cancer cells of SRP-6, making those cells easier to kill.
“The next piece of this puzzle will be to find compounds that either activate or block SRP-6,” said Barstead. “If researchers can identify compounds that target this protein, it will put us a step closer to effective therapies for many life-threatening human illnesses.”
The research was led by Cliff Luke, Ph.D., and Gary Silverman, M.D., Ph.D., at the University of Pittsburgh and funded by the National Cancer Institute, the National Human Genome Research Institute, the Mario Lemieux Foundation and the Twenty-Five Club of Magee-Womens Hospital at the University of Pittsburgh Medical Center.
OMRF (omrf.org) is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human disease. Chartered in 1946, its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease.