By screening nearly 250 factors in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS), Chinese researchers were able to identify a marker linked to disease severity. The team also found a protein that distinguished ALS from other neurological diseases which, if confirmed in larger studies, could act as a potential biomarker for disease diagnosis.
The study, “Proteomic analysis of cerebrospinal fluid in amyotrophic lateral sclerosis,” was published in the journal Experimental and Therapeutic Medicine.
The researchers at Fudan University in Shanghai, China, recruited 35 ALS patients along with two different control groups to tease out factors that are specific to ALS, using a high throughput method to analyze a large number of factors in a single sample. One control group consisted of patients with tension headaches but considered neurologically healthy. The other group included patients with various other neurological conditions.
The screening was successful and the team found 14 proteins present in higher levels and 21 in lower levels among ALS patients, compared to people in the control groups. Analysis of the biological function of these factors revealed they were mostly involved in inflammation, response to tissue damage, and other immune functions.
Three of these proteins were randomly chosen to be verified by another method for protein analysis, confirming two factors to be altered among ALS patients compared to both healthy people and patients with other neurological conditions.
Researchers then took the two proteins found in higher levels — IGF-2 (insulin‑like growth factor 2) and GRIA4 (glutamate receptor 4) — through extensive testing to see if the factors could be linked to disease characteristics.
It turned out that GRIA4 levels were higher in men. Also, higher concentrations were found mostly in patients with less severe disease, indicating that the factor could be used as a reference for guiding treatment choices.
IGF, on the other hand, was not linked to any disease characteristics, leading researchers to suggest that low levels of the factor might be used as a diagnostic aid for ALS.
ALS is not easy to diagnose given its similarity to other neurological conditions. Physicians today rely on a number of tests, including brain scans, muscle biopsies, and analyses of blood, urine, and cerebrospinal fluid. Finding biomarkers of ALS — biological factors that can distinguish an ALS patient from other types of neurological conditions — would greatly improve diagnosis and disease management.
In addition to the Chinese research group, scientists from around the world are using various screening methods to search for biomarkers of ALS, a research area supported by the ALS Association.