Proteins in CSF May Be Biomarkers of Diagnosis, Treatment Response

Cerebrospinal fluid analysis may provide 'robust biomarkers for clinical trials'

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
csf biomarkers | Friedreich's Ataxia News | illustration of person on computer

Some proteins in the cerebrospinal fluid (CSF) — the fluid that flows around the brain and spinal cord — are present in unusual amounts in patients with Friedreich’s ataxia, and may be candidate biomarkers for diagnosis, a small study suggests.

Researchers found that the proteins are involved in how nerve cells stop working or die (neurodegeneration) and in the inflammatory response within the brain and/or spinal cord (neuroinflammation).

“Neurodegeneration and neuroinflammation are processes that may respond to treatment, so at least some of these [proteins] may turn out to be treatment response biomarkers in addition to diagnostic biomarkers,” the researchers wrote.

The study, “Cerebrospinal fluid proteomics in Friedreich ataxia reveals markers of neurodegeneration and neuroinflammation,” was conducted by a team of researchers in Belgium and published in Frontiers in Neuroscience.

Recommended Reading
fat molecules such as ceramides | Friedreich's Ataxia News | illustration of scientist working in lab

Metabolic Markers May Help in FA Diagnosis, Therapeutic Development

Patients with Friedreich’s ataxia have a shortage of frataxin, a protein that controls how much iron there is in mitochondria (the energy-making factories of cells). As a result of this shortage, iron builds up inside cells, which prevents mitochondria from making enough energy. It also makes cells more sensitive to certain forms of oxygen (reactive oxygen molecules) that cause damage. When this happens to cells in the brain, spinal cord, and muscles, symptoms of Friedreich’s ataxia can occur.

While there is no cure for the disease, some treatments may help ease its symptoms. Several experimental treatments are being studied, but not many patients can make it into clinical testing, and biomarkers may be unavailable to quickly monitor the response to treatment.

This means that clinical trials “offer special challenges, particularly when multiple treatments become ready for clinical testing,” the researchers wrote. Thus, the researchers went on the lookout for new biomarkers that could offer a reliable way to monitor the response to treatment.

The team focused on the CSF, which is known to contain small amounts of a range of proteins that may respond to changes in disease status.

How was the study conducted?

The study included five patients with Friedreich’s ataxia (four women and one man) who experienced their first symptoms at an age ranging from 7 to 23 years. They had the disease for up to 45 years, and three of the women used a wheelchair to get around. The researchers got CSF samples through the European Friedreich’s Ataxia Consortium for Translational Studies.

To collect a CSF sample, doctors need to perform a lumbar puncture, also known as a spinal tap, which involves inserting a thin needle into the lower spine. It is not usually part of the diagnostic workup for Friedreich’s ataxia.

The team used CSF samples from 19 individuals (12 women and seven men) who had a lumbar puncture as part of a diagnostic workup and who served as the control group. Their median age was 33 years, with ages ranging from 20 to 62. Most (15 individuals) received a final diagnosis of headache; three had a functional neurological disorder, and one had idiopathic intracranial hypertension (a high pressure around the brain without a known cause).

To be able to tell which proteins were present in different amounts in patients versus controls, the researchers used a technique called liquid chromatography coupled with another one called mass spectrometry. Then, with the help of a special computer software tool, called ProteinPilot, they were able to identify these proteins and their amounts.

Recommended Reading
inheritable disabilities | Friedreich's Ataxia News | main graphic for column titled

Making My Story Dynamic, Part II: Rewriting My Diagnosis Story

In total, there were 92 proteins present at significantly higher levels in the CSF of patients than in controls, and 80 proteins present at lower levels.

For seven of the proteins with increased levels and six of those with decreased levels, there was no overlap between patients and controls, “suggesting that these may be potential biomarkers for clinical studies.”

Two of the proteins with increased levels, SORCS3 and SCG5, have their highest levels in the brain and have been linked to neurodegeneration.

Of those with decreased levels, there were three — CNDP1, ISLR, and NRXN2 — with roles in how the extracellular matrix is put together to support and give structure to cells. Three others — CD14 and the complement factors C3 and C9 — play a part in the immune response and neuroinflammation.

Overall, while the study included a small number of patients, it “supports the hypothesis that the quantitative analysis CSF proteins may provide robust biomarkers for clinical trials as well as shed light on pathogenic mechanisms,” the researchers concluded, adding, however, that these findings “need validation with specific protein assays” and with clinical and genetic data.