PROJECT A.L.S.-funded researchers at Brigham and Women's Hospital (BWH) have identified the process in which the antibiotic minocycline, commonly prescribed for acne, inhibits the progression of cell death in the brain that causes amyotrophic lateral sclerosis (ALS), a debilitating and ultimately fatal neurological condition also known as Lou Gehrig's Disease. The findings of the study, which was funded by a grant from the science-based organization Project ALS, are published in the May 2nd issue of the journal, Nature.

"Building on the knowledge that minocycline has numerous neuroprotective properties, we found the specific steps in which this drug blocks a key trigger of the cell death pathway," said Robert M. Friedlander, MD, of BWH and senior author of the study. "Minocycline is a safe drug that when taken orally reaches the brain, indicating that the drug may provide a new treatment for ALS patients."

In the study, which used mouse models, researchers found that minocycline blocks the release of the cellular protein cytochrome c into the cell's cytoplasm. Once cytochrome c is in the cytoplasm, it is known to activate the enzyme caspase-3. When activated, the caspase-3 enzyme enables cells -- especially motor neuron cells in the brain -- to commit suicide. Therefore, while minocycline doesn't directly inhibit the cell-killing caspase-3 enzyme, it does interfere with the cell death pathway at an early stage.

Patients with ALS do not experience any cognitive decline, but they do experience progressive physical debilitation including paralysis and motor deterioration. The life expectancy of an ALS patient averages only three to five years following the onset of these symptoms. The cause of the disease is unknown in most patients, although ALS currently affects approximately 50,000 individuals in the United States. The total number of ALS patients continues to grow as nearly 5,000 new cases of the disease are diagnosed each year. The only proven therapy for humans currently is the drug riluzole, which extends survival in humans approximately three months.

"By understanding the mechanism by which minocycline prevents cell death, we can better target ALS treatment," added Dr. Friedlander. "We now need to test combinations of minocycline and other drugs to create a drug "cocktail" that would be a safe, powerful therapy for ALS patients."

In addition, the study's findings may have implications on more conditions than just ALS. According to Dr. Friedlander, the process which initiates cell death leading to ALS is similar to that in other neurological diseases such as Huntington's, Parkinson's and Alzheimer's diseases as well as injuries such as stroke, traumatic spinal cord and brain damage.

"Minocycline has already been shown to be effective in animal models of Huntington's disease, stroke, traumatic brain injury and Parkinson's disease," said Dr. Friedlander. "Now we know how it works, and this will enable us to develop more effective therapies for these devastating and often untreatable diseases."

The study was funded in part by the Huntington's Disease Society of America, the Hereditary Disease Foundation and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

Project A.L.S. Background:

Project A.L.S. is a science-based non-profit 501C(3) organization dedicated to finding and funding the most promising ALS and related research worldwide. It is a condition of Project A.L.S. funding that scientists from a variety of disciplines work together, in a coordinated, concerted, and committed fashion toward an understanding and treatment of ALS. Also known as Lou Gehrig's disease, ALS is a uniformly fatal neurodegenerative disease that is closely related to Parkinson's, Alzheimer's and Huntington's, and that does not discriminate on the basis of age, gender or ethnicity.

BWH Background:

BWH is a 716-bed nonprofit teaching affiliate ofHarvard 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.

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For more information

CONTACT: Mario Ruiz of Dan Klores Communications, +1-212-981-5156, for PROJECT A.L.S.