November 18, 2020

Biomarkers On the Brain: Putting Biomarkers Together for a Better Understanding of the Nervous System

Biomarkers for neurological diseases used to be few and far between, but better technology is making it easier for researchers to track brain health by measuring molecules. This means less invasive testing, earlier diagnosis, faster drug development, and—hopefully—more effective treatments.

Biomarkers—molecules that indicate the presence of a disease or dysfunction—are becoming increasingly instrumental for confirming diagnoses, choosing the best treatments, and monitoring disease progression. One exception is biomarkers for neurological conditions. Neurological biomarkers are present in cerebral spinal fluid (CSF), but rarely—or at undetectable levels—in blood. The brain is closely protected by its own private “security guard,” the blood–brain barrier, which shields it from harmful substances circulating in the bloodstream. Unfortunately for diagnostic purposes, this barrier has also made the brain’s chemistry inaccessible to a convenient blood test. Neurological biomarkers can be studied using CSF, but this requires an invasive and painful lumbar puncture procedure.

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Image Credit: sciencemag

Central Nervous System (CNS) biomarkers are used to check clinical utility and to help decisions regarding particular drug treatment, and if it is effective, it is most likely to receive reimbursement from the regulatory advisor. These biomarkers are valuable because they could be implemented as diagnostic screens for several diseases, as it would be less invasive for patients.

However, these elusive neurological biomarkers are now coming into view. Recent advances in detection, as well as the comprehensive power of clusters of biomarkers, or biomarker signatures, are making the brain more accessible and neurological diseases more treatable. Diagnosing and treating neurological disorders—such as chronic traumatic encephalopathy (CTE), Alzheimer’s disease, Parkinson’s disease, autism, and major depressive disorder—is likely to become easier with the recent advent of neurological biomarkers detected in blood.

The recent ability to detect neurological biomarkers in the blood is due in part to technological advances in detection. For example, Quanterix’s Simoa (single-molecule array) technology bumps up sensitivity by digitizing an ELISA (enzyme-linked immunosorbent assay), a highly effective method of determining binding between two molecules. Quanterix screens patient samples with 720,000 microscopic beads coated with capture antibody (for the biomarker of interest), incubates the beads with a capture antibody and mixes them with a fluorescent marker, then spreads the beads into 216,000 isolated microchambers. The resulting high signal-to-noise ratio makes for very responsive detection.

About half of Quanterix’s current applications are linked to neurology, and many researchers using their platform measure biomarker concentrations in both CSF and blood. “Typically, we see a concentration difference of about 1:100 or 1:500, so we think it’s a breakthrough to now be able to look at brain health noninvasively,” says Kevin Hrusovsky, CEO of Quanterix in Lexington, Massachusetts. “We can see a single femtogram per mL of a biomarker, which is sensitive enough to detect biomarkers in saliva and breath condensate as well.”

References:

https://www.theinsightpartners.com/reports/central-nervous-system-biomarkers-market

https://www.sciencemag.org/features/2017/12/biomarkers-brain-putting-biomarkers-together-better-understanding-nervous-system