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Protein biomarkers accurately and quickly diagnose ALS, find Pittsburgh researchers


Proteomic signature for ALS identified

Detection of protein abnormalities in cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) may allow physicians to more rapidly diagnose and better monitor drug efficacy in clinical trials for the disease, according to a novel study presented by a University of Pittsburgh researcher in Milan, Italy, today.

These findings may lead to the first test for early stage ALS, also know as Lou Gehrig’s disease.

The study, presented by Robert Bowser, Ph.D., of the University of Pittsburgh School of Medicine at the 11th annual meeting of the International Alliance of ALS/MND Associations and 14th International Symposium on ALS/MND, identified ALS-specific biomarkers by protein profiling of cerebrospinal fluid from 25 ALS patients and 35 control subjects.

"There are no known diagnostic biomarkers for ALS and no sensitive methods to determine whether a particular drug is working in an ALS patient, nor any way to best test drug combinations for effectiveness," said Dr. Bowser, who is associate professor of pathology and director of the ALS Tissue Bank at the University of Pittsburgh School of Medicine. "A panel of biomarkers would not only be useful in a more rapid diagnosis of ALS, but also would be a valuable tool to evaluate drug efficacy in clinical trials. Protein profiling may also identify biochemical pathways leading to cell death and new therapeutic targets."

CSF samples were obtained from recently diagnosed ALS patients and control subjects who did not have ALS. Some control subjects had no neurologic symptoms, while others had neurological diseases (including four with peripheral neuropathies, one with myopathy, one with probable Alzheimer’s, one with demyelinating disorder, one with meningitis and one with autoimmune sensory motor axonopathy). CSF was used because it is in close contact with motor neurons and brain cells called glia affected by ALS and therefore may harbor high concentrations of diagnostic biomarkers.

Using mass spectrometry to characterize protein peaks that exhibit statistically significant alterations between ALS patients and the control groups, Dr. Bowser and his colleagues identified protein biomarkers that diagnose ALS with near 100 percent specificity and sensitivity.

"Not only will a CSF-based test lead to faster diagnosis, it will permit physicians to monitor the patient during drug treatment and determine whether any of the protein abnormalities that have occurred in the patient have been reduced due to drug treatment. By monitoring the biomarkers, we will be able to directly monitor drug efficacy. By using data from multiple clinical trials, we can determine the best drug combination to offer ALS patients," Dr. Bowser said.

"This research is at the forefront of ALS research. Our next step is to confirm our results with a larger patient population and further evaluate how the biomarker signature pattern changes during disease progression," he said.

The International Symposium on ALS/MND brings together leading international scientists, clinicians and health and social care professionals to present and debate key innovations in their respective fields. The symposium is planned as two parallel meetings, one on biomedical science and the other on research and advances in the care and management of people affected by ALS/MND.

Dr. Bowser’s research is in collaboration with investigators at Massachusetts General Hospital/ Harvard.

ALS is a fatal neurodegenerative disease that attacks nerve cells and pathways in the brain and spinal cord. When cells die, voluntary muscle control and movement is lost. Those patients in the later stages of the disease are totally paralyzed even though their minds remain alert. The average life expectancy of a person with ALS is between two to five years from time of diagnosis.

Frank Raczkiewicz | EurekAlert!
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