Blood NfL Levels Seen as Sensitive Marker of FAP and Its Progression

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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NfL as blood biomarker

Levels of neurofilament light chain (NfL) — a proposed biomarker of several neurological disorders — are significantly higher in people with familial amyloid polyneuropathy (FAP) who show symptoms, compared to those who are asymptomatic or healthy, a study reported.

Plasma (blood) levels of NfL (pNfL) were also significantly associated with disease severity and duration, and able to classify patients in the early disease stages with high accuracy.

Blood levels of this marker were sensitive enough to support its use in trials judging the effectiveness of potential FAP treatments, the researchers said. 

The study, “Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy,” was published in the journal Amyloid

FAP, also called transthyretin amyloid polyneuropathy (ATTR), is caused by mutations in the TTR gene, leading to abnormal clumping of proteins in nerves and other tissues.

In the early stages of FAP, people may not experience symptoms. And those who do cannot be easily assessed using objective and rapid measurements.

Finding a reliable biomarker for FAP would not only support clinical trials, but also help identify those in early stages of the disease. 

Researchers at the Universidade do Porto, in Portugal, and colleagues in Italy and Switzerland, wondered if pNfL — a marker of nerve cell damage — could be a useful biomarker for FAP. Notably, elevated levels of pNfL have been found in such neurological disorders as multiple sclerosis and amyotrophic lateral sclerosis.

Blood samples were collected from patients in Portugal and Italy, who were investigated separately. Of those in Portugal, three people were excluded due to lack of clinical data, as were five in Italy because medicines they were taking could have affected results.

Overall, the study included 60 people with the V30M mutation — the most prevalent TTR gene mutation. Forty-four patients had FAP symptoms, while 16 did not (asymptomatic patients, also known as carriers).

Sixteen other people, either healthy relatives of patients or volunteers from the same region, were included and served as controls.  

Disease severity was assessed using the Polyneuropathy Disability Score (PND), which classifies patients into six stages (0, 1, 2, 3a, 3b, 4). Those at stage 0 have no impairments, while patients at stage 4 needed a wheelchair or are bedridden. 

Results from the Portugal group (42 patients) revealed that pNfL levels were higher in symptomatic patients (PND of 1 or above) compared to healthy controls.

Levels of pNfL in people at stage 1 PND were almost five times higher than in asymptomatic patients, and those at stage 2 or above were more than 15 times higher.

In both groups, the increase in pNfL followed a linear trend, being higher in people with more severe disease. This was independent of  patients’ age or gender. In turn, no differences in pNfL levels were found between asymptomatic patients and healthy relatives. 

In the Portugal group, higher pNfL levels were associated with longer disease duration, which was not demonstrated in the group from Italy. 

A comparison of asymptomatic patients to those with symptoms found that assessing pNfL levels was able to discriminate between these two groups with a sensitivity of 96.2% and a specificity of 93.8%. While sensitivity refers to the ability to correctly identify patients with a condition, specificity is the accurate identification of people without a given disorder or complication.

The test was also able to distinguish patients at stage 0 from those in early disease stages, and between those with early symptoms at stage 1 and patients at stage 2, who have signs of motor dysfunction. 

“pNfL is an easily accessible biomarker to establish ATTR-V30M disease conversion and to monitor disease progression,” the researchers wrote. “pNfL could be used as efficacy measure of disease-oriented therapies in clinical and pre-clinical trials.”