Researchers at Brigham and Women's Hospital (BWH) and Children's Hospital Boston (CHB) have found that a commonly prescribed antibiotic could be used to help prevent paralysis and other long-term functional deficits associated with a partial spinal cord injury (SCI). Researchers in the field have known that a significant proportion of paralysis and long-term functional disorders associated with SCI are triggered by post-trauma tissue loss. Administering the antibiotic, minocycline, to rats within the first hour after a paralyzing injury has been shown to reduce this tissue loss and ultimately enable more hind-leg function, the ability to walk with more coordination, better foot posture and stepping, and better support of body weight than untreated controls. The findings are published in the March 2, 2004 issue of the Proceedings of the National Academy of Sciences.
The BWH/CHB researchers found that minocycline reduces later-stage tissue loss by blocking release of a protein known as mitochondrial cytochrome c. Yang D. Teng, MD, PhD, of the joint BWH/CHB neurosurgery program and co-lead author of the study, notes that other experimental agents can prevent later-stage tissue loss, but must be given immediately after or even before SCI to be effective. "The field has badly needed to develop a drug that could be used in a practical manner," said Teng.
According to the National Spinal Cord Injury Association, approximately 250,000 to 400,000 individuals in the United States currently have spinal cord injuries with more than 11,000 individuals each year impacted by a spinal cord injury. Ninety percent of these injuries are partial – meaning that the spinal cord is damaged but not severed, as in the current study.
"These research results are exciting in that they demonstrate a novel post-trauma strategy in the form of a safe, FDA-approved drug that could serve as a prototype drug for developing better therapeutic strategies to improve quality of life for people suffering from spinal cord injuries," said Teng, also an assistant professor of Surgery at Harvard Medical School (HMS).
The steroid methylprednisolone is currently used for SCI in clinical practice, but is falling into disfavor because of severe side effects. Minocycline, a well-known neuroprotector that is currently being tested to treat stroke, ALS, Huntington's disease and head trauma, has no observable side effects in the rat model and can be given for up to an hour after SCI, providing a more realistic timeframe for clinical use.
"We believe that if minocycline is demonstrated effective in clinical trials of SCI, it will likely be part of a comprehensive cocktail of medications targeting the acute and chronic injuries of this devastating disease," said Robert M. Friedlander, MD of BWH, HMS associate professor of Neurosurgery and co-lead author of the study. "Because minocycline has already been proven as an effective neuroprotector and is capable of penetrating the blood-brain barrier, we believe that it may become the next-generation therapy for treating SCI."
Also collaborating in this study was the VA Boston Healthcare System, where Teng is director of spinal cord injury research.
BWH is a 725-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, BWH is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital's preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, BWH conducts internationally acclaimed clinical, basic and epidemiological studies.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults for more than 130 years. More than 500 scientists, including seven members of the National Academy of Sciences, nine members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Children's research community. Children's is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital visit: http://www.childrenshospital.org
Materials provided by Children's Hospital Boston. Note: Content may be edited for style and length.
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