CXCL12 levels in spinal fluid may improve ALS diagnosis accuracy
Protein biomarker levels may help differentiate ALS from other conditions
Measuring the levels of a novel protein biomarker called C-X-C motif chemokine ligand 12 — CXCL12 for short — in the spinal fluid may improve the diagnosis of amyotrophic lateral sclerosis (ALS) by better differentiating it from similar conditions, according to a new study.
In particular, the protein may be used in combination with neurofilament light chain (NfL), a well-known biomarker of nerve damage. While NfL can distinguish ALS patients from healthy people with great accuracy, CXCL12 is better at discriminating the disease from other neurological conditions, the study found.
“Larger studies are needed to validate these results, but [CXCL12] determination shows promising diagnostic potential,” the researchers wrote.
Titled “Increased CXCL12, a potential CSF biomarker for differential diagnosis of amyotrophic lateral sclerosis,” the study was published in Brain Communications.
Up to 10% of patients with an ALS diagnosis actually have a mimic disease
Diagnosing ALS is a complex process that involves testing for signs indicative of the disease and excluding other conditions with similar symptoms. This typically requires many different tests, thus patients usually wait about one year from their first symptoms until an ALS diagnosis is confirmed.
Still, it’s estimated that up to 10% of patients who are initially diagnosed with ALS actually have an ALS-mimic disease, which has distinct treatment options and often a different prognosis. It’s therefore critical that better tests are developed to discriminate between these conditions, to ensure a correct diagnosis of ALS and potentially bring effective treatments to all patients sooner.
In recent years, NfL has emerged as a promising biomarker for ALS and many other neurological conditions. The protein is part of nerve cells’ cytoskeleton, and gets released into the surrounding fluids when nerves are damaged. Therefore, an increase in NfL levels in the cerebrospinal fluid (CSF) — the fluid that surrounds the brain and spinal cord — or blood is usually a good indicator of increased nerve damage.
However, while this protein can usually distinguish people with neurological diseases from healthy people, it’s not very good at discriminating the different neurological diseases from each other.
“Increased levels of [NfL] in the CSF are not specific to the disease, being increased in most of the neurological conditions,” the team wrote.
CXCL12 could be used alongside NfL to improve diagnostic process
CXCL12 is a molecule that attracts and retains immune cells in specific tissues. It’s also involved in the development and maintenance of the immune system, and facilitates the formation of blood vessels. Further, the molecule has a role in the regeneration of the nervous system after injury.
In an earlier study, a team of researchers in Spain had identified CXCL12 as a potential biomarker of ALS — namely of the neuroinflammatory response that occurs in people with this neurodegenerative condition. Now, they set out to determine if this molecule could be used to complement NfL as a diagnostic biomarker of ALS.
In their new study, the team measured the levels of both proteins in CSF samples from 48 people with sporadic ALS, the name given when the disease occurs spontaneously. These levels were compared with those of 68 healthy controls and 42 patients with ALS-mimic disorders, such as myelopathy and inflammatory polyneuropathy.
The results showed that both CXCL12 and NfL levels in the CSF were very good at distinguishing people with ALS from healthy controls. However, CXCL12 levels in CSF were much better than NfL at discriminating ALS from the mimic conditions. The accuracy was greater than 95% when CXCL12 levels were used to distinguish between conditions, while it ranged between 69% and 92% when NfL was used.
Our results are not intended to displace the use of [NfL] in CSF, but rather to complement it. … [CXCL12 is] a new clinical tool candidate.
The team also examined the potential of using CXCL12 levels in plasma, the liquid portion of blood, as a less invasive diagnostic tool. But the diagnostic accuracy was much lower than that observed for CSF samples, suggesting that spinal fluid testing remains a more reliable method for diagnosing ALS.
Overall, the findings suggest that using CXCL12 alongside NfL could improve the diagnostic process for ALS, helping to distinguish it from similar conditions more accurately and helping get a more accurate diagnosis.
“Our results are not intended to displace the use of [NfL] in CSF, but rather to complement it,” the researchers wrote, calling CXCL12 “a new clinical tool candidate.”
The findings could pave the way for better diagnosis and management of ALS and related conditions in the future. A new understanding of ALS “and potential therapeutic targets or surrogate markers for treatment response” are some areas CXCL12 can open beyond its use as a biomarker, according to the researchers.
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