WASHINGTON, D.C.--Amyotrophic lateral sclerosis (ALS) ravages neurons in the brain and spinal cord, often killing sufferers within five years. But diagnosing the disorder remains a major challenge. Now, a pilot study presented here 18 April at the Federation of Societies for Experimental Biology meeting has identified 10 proteins that can distinguish ALS patients from healthy individuals.
Doctors lack "biomarkers" with which to definitively identify ALS patients. Biomarkers are proteins or other molecules that can help diagnose or track progression of disease; one example is prostate-specific antigen, the biomarker used to detect prostate cancer. Without ALS biomarkers, doctors and patients cannot be certain until defining symptoms, such as muscle weakness and speech problems, appear. This can delay treatment or lead to faulty diagnoses.
Pathologist Robert Bowser of the University of Pittsburgh in Pennsylvania and his colleagues decided to hunt for ALS biomarkers in the cerebrospinal fluid, which is in intimate contact with the neurons and glial cells that ALS destroys. They gathered samples from 25 ALS patients, who on average had had symptoms for about a year, and 35 controls. About half the controls were healthy; the other half had diseases, including Alzheimer's disease and neuropathies, which sometimes present with ALS-like symptoms.
By exhaustively analyzing the protein content of the samples, Bowser's team found 10 proteins whose levels were consistently higher or lower than those in controls. The group then analyzed a separate set of 32 samples, including 15 from ALS patients, without knowing which samples were from ALS patients and which weren't. Using an algorithm they'd crafted to distinguish the biomarker patterns, they correctly identified 12 of the 15 ALS samples and an even higher percentage of controls. In addition to early diagnosis, Bowser hopes that his biomarkers will shed light on the disease; at least one of the proteins falls in a pathway that ALS destroys.
"It's very exciting," says Lucie Bruijn, science director of the ALS Association. But she cautions that the results are preliminary. The association recently gave Bowser funds for an expanded study, to see whether the biomarkers hold up in a larger population.