BOSTON - September 25, 2002 - Why do some nerve cells survive and regrow after injury while others shrink away and die? A new discovery by researchers at Massachusetts General Hospital (MGH) shows that the expression of a particular gene may be responsible for protecting neurons from death. The results, published in the September 26 issue of Neuron, could lead the way for new treatment strategies for a variety of neurological diseases.
"Turning on the gene named Hsp27 could potentially rescue nerve cells in patients with neurodegenerative conditions such as Lou Gehrig's disease," says principal investigator Clifford Woolf, MD, PhD, of the Neural Plasticity Research Group in the Department of Anesthesia and Critical Care at MGH.
Woolf and his colleagues found that young sensory and motor nerve cells die after injury because the heat shock protein 27 gene (Hsp27) is not turned on in these cells. In adult cells however, the gene is expressed. The resulting protein that is produced protects these mature nerve cells from death following an injury.
"As part of normal development, many more neurons are made than are needed," says Woolf, who also is Richard J. Kitz Professor of Anesthesia Research at Harvard Medical School. "So some must be pruned away by essentially committing cell suicide, a phenomenon known as programmed cell death. It seems that Hsp27 is turned off to allow for this normal developmental process."
Woolf explains that once an individual reaches adulthood, nerve cells in the body are permanent and irreplaceable. "That's why it's important to have a repair mechanism for older neurons," he says. The protein made by the Hsp27 gene blocks cell suicide from taking place following injury, rescuing injured cells. For example, cells expressing the Hsp27 protein acquire resistance to excessive heat, chemical stress, and toxins. Hsp27 directly inhibits the cellular proteins that trigger programmed cell death.
In laboratory dishes and in rat models, Woolf and his team showed that, if the Hsp27 gene is delivered to young nerve cells using gene therapy with viral vectors, the cells are able to survive injury just as well as older nerve cells. Equally, if the gene is switched off in adults, those cells will die. "Hopefully, therapy that prevents cell death by delivering genes like Hsp27 will someday find its way into the clinic," says Woolf. "Patients with Lou Gehrig's disease, for example, suffer a progressive death of their motor neurons leading to paralysis. If Hsp27 were able to prevent the death of the neurons in these patients, it would offer the possibility of new therapy, something we plan to test"
The other members of the MGH research team are Susanna Benn, Ph.D, first author, Joachim Scholz, MD, and Richard Mannion, MD, PhD - all of the MGH Neural Plasticity Research Group - and Joanna Bakowska, DVM, PhD, of the Molecular Neurogenetics Unit at MGH. The study was supported by grants from the National Institutes of Health and the Alexander von Humboldt Foundation.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine.
In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.
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