A University of Pittsburgh pathologist has identified the first protein biomarkers able to diagnose patients with amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) with near 100 percent accuracy. Before this finding, there were no known diagnostic biomarkers for this neurodegenerative disease.
As a result, diagnosis typically takes from six to 12 months after patients first experience neurological symptoms, all of which could be caused by a number of neurological diseases and disorders. Although ALS is always fatal, usually between two to five years following diagnosis, diagnostic delay of this magnitude may limit the potential benefit of the one drug that has been approved by the FDA for ALS, a drug shown to provide maximal benefit if taken as soon as possible following the onset of the disease.
Dr. Robert Bowser presented his findings at Experimental Biology 2004, as part of the scientific sessions of the American Society of Investigative Pathology (ASIP). 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 are lost. Patients in the later stages of the disease are totally paralyzed although their minds remain alert.
To identify the specific ALS biomarkers that could be used as a diagnostic tool, Dr. Bowser and his colleagues examined the cerebrospinal fluid (CSF) from 25 people recently diagnosed with ALS and 35 control subjects without ALS. Some of the controls had no neurological symptoms and some had other neurologic diseases that present to the physician with symptoms similar to ALS, including muscle weakness and loss of motor function. He chose CSF because the fluid is in intimate contact with the motor neurons and glia affected during ALS and he believed it was most likely to contain the highest level of protein biomarkers.
He was right. Using mass spectrometry, the researchers identified 10 protein biomarkers that differentiated between the ALS patients and the non-ALS patients. When the scientists looked at the proteins themselves, they found statistically significant differences in 13 percent of the protein peak intensities between ALS and non-ALS patients. But using the new proteomic technology and two different and complex computer algorithms, they were able to identify a series of protein peaks – a pattern – that produced a high level of sensitivity (accurately identifying all the ALS patients) and specificity (avoiding false positives among the non-ALS patients). These protein peaks represent the first biomarkers for ALS – and could be completed within a few hours instead of the months now demanded.
The next step, says Dr. Bowser, is to confirm these results in a larger patient population so that the protein biomarkers can be used as a rapid diagnostic test for ALS, allowing patients to initiate treatment at the time of onset. ALS patients are now being enrolled in a large collaborative study funded by the ALS Association.
The study also will permit the researchers to evaluate how the biomarker signature pattern may change during disease progression. This will help clinicians monitor drug effectiveness in clinical trials to find new and improved treatments for ALS. Also underway in Dr. Bowser's lab are efforts to determine the protein identity of each biomarker. This will provide new insight into the biochemical pathways that cause ALS and, he believes, indicate novel targets for drug therapy.
Dr. Bowser's co-authors for the Experimental Biology 2004 presentation, include Dr. Srikanth Ranganathan and Dr. Billy W. Day, from the University of Pittsburgh; and Merit E. Cudkowicz and Robert H. Brown, Jr., from Massachusetts General Hospital and Harvard University. In addition to these scientists, other collaborators in the ongoing ALS Association study include Dr. Cudkowicz from Massachusetts General Hospital/Harvard and Dr. Kaddurah-Daouk at Metabalon, Inc.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.
Affirmations are like prescriptions for certain aspects of yourself you want to change.
-- Jerry Frankhauser