BOSTON, MA--Researchers from Brigham and Women's Hospital (BWH) are the first to discover that changes in monocytes (a type of white blood cell) are a biomarker for amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. This finding also brings the medical community a step closer toward a new treatment for the debilitating neurological disease that affects approximately 30,000 Americans.
The study will be published online in The Journal of Clinical Investigation on August 6, 2012.
In pre-clinical studies involving mice with an ALS gene mutation, the researchers saw that two months prior to ALS onset, monocytes in the spleen began exhibiting proinflammatory qualities. As disease onset loomed, there was an increase in cell-signaling molecules that directed monocytes to flood the spinal cord. Influx of these inflamed white blood cells was associated with nerve cell death in the spinal cord.
When the researchers treated the mice with antibodies to modulate the inflammatory monocytes, they found that it led to fewer monocytes entering the spinal cord, diminished nerve cell loss and extended survival.
After having observed these activities in mice, the BWH researchers, working with the Massachusetts General Hospital (MGH) ALS Clinic and research team, found that there were similar monocytes in humans with ALS that also exhibited a disease-specific inflammatory signature.
"People have wondered if the immune system plays a role in neurological diseases like ALS," said Howard Weiner, MD, director of the BWH Multiple Sclerosis Program and senior study author. "The immune system is complicated, and previous immunotherapy trials have not been successful. But now we know what is wrong in the blood, and this opens up new therapeutic targets for ALS and perhaps other diseases in the near future."
Study co-author Merit Cudkowicz, MD, who heads the ALS program at MGH adds, "These findings identify a potential new target for developing treatments for people with ALS."
Oleg Butovsky, PhD, BWH Department of Neurology is first study author and lead scientist on the study.
Each year, approximately 5,600 people in the United States are diagnosed with ALS, a disease that affects nerve and muscle functioning, eventually leading to paralysis. The average age at diagnosis is 55 years old and half of those affected live at least three or more years after being diagnosed. Twenty percent live five years or more, and up to 10 percent will live more than ten years.
This research was supported by the Amyotrophic Lateral Sclerosis Association, National Institutes of Health (AG027437), Prize for Life, and the Tufts Center for Neuroscience Research.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
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