Proteins mark ALS.

Today, physicians diagnose people with amyotrophic lateral sclerosis (ALS)--better known as Lou Gehrig's disease--by process of elimination. In a series of exams that can last a year, a doctor must rule out other neurological diseases with similar symptoms, such as muscle weakness or slurred speech. A University of Pittsburgh pathologist now reports finding a perturbed pattern of proteins--some elevated, others abnormally low--in the cerebrospinal fluid of ALS patients. Computer analysis of these proteins permits diagnosis of ALS in a day, with 86 percent accuracy, says Robert Bowser.

Bowser says that this diagnostic pattern of up to 10 proteins "changes as the disease progresses." Periodically checking the pattern during trials of new drugs might provide the first quantitative way to gauge how experimental therapies affect progression of the disease.

The one federally approved drug for the disease "offers only minor benefits" Bowser notes. ALS usually kills a person within 5 years of the diagnosis.

The basis for the new ALS test emerged after Bowser measured the molecular sizes of the proteins in cerebrospinal fluid of 30 people with ALS and 30 others who were healthy or had a neurological disorder other than ALS. The difference in the two groups was clear, says Bowser, but the test's accuracy should increase as more individuals are included in the database. Moreover, he adds, as further research identifies all the proteins and their functions, drug designers will get better clues about where to target new ALS therapies.--J.R.