Blood protein NfL may be useful marker of disease activity in FAP
But its utility may vary depending on each patient's underlying mutation
Levels of a blood protein called NfL may be useful as a marker of disease activity in people with familial amyloid polyneuropathy (FAP), a new study reports — though the utility of this biomarker may vary depending on each patient’s underlying gene mutation, according to the researchers.
While the study involved a small number of participants, the scientists noted that “these findings are especially relevant for patients [younger than] 60 without comorbidities,” or other coexisting conditions.
“Future studies should expand the [patient group] to include more participants and a broader range of treatment,” the team wrote.
Nonetheless, the researchers concluded: “Our study confirms the reliability of NfLs as [a] promising biomarker for assessing disease activity levels and progression rate.”
Titled “NfL as a biomarker in ATTRv amyloidosis: potential and limitations,” the study was published in the journal Neurological Sciences.
Data confirm NfL protein as ‘promising biomarker’ for progression rate
A genetic disease, hereditary transthyretin amyloidosis (ATTRv) is caused by mutations in the TTR gene. FAP — the most common form of ATTRv — is characterized by neuropathy, or nerve damage, that leads to symptoms such as abnormal sensations, weakness, and problems with coordination.
People with FAP also commonly experience autonomic impairment, or problems regulating unconscious bodily functions like heart rate and digestion.
NfL, short for neurofilament light chain, is a protein that’s normally found in nerve fibers. When nerves are damaged, NfL tends to leak out. As such, NfL levels in the blood are often used as a biomarker of nerve damage.
In this study, a team led by researchers at the University of Messina in Italy examined the utility of NfL for tracking disease activity in FAP.
“Our objective was to determine whether NfL could serve as a reliable biomarker for disease activity,” the scientists wrote.
The researchers analyzed blood samples from 28 people with symptomatic ATTRv as well as eight presymptomatic carriers who had TTRÂ mutations but did not have any symptoms of the disease. Blood samples from 27 people without TTR mutations also were analyzed. For the symptomatic patients, blood samples were collected at an initial visit, then again six months and one year later.
The results showed that average NfL levels were significantly higher in symptomatic patients than in presymptomatic carriers or people without TTR mutations. NfL levels showed no difference between presymptomatic carriers and people without TTR mutations, the researchers noted.
Among the ATTRv patients, there were significant correlations between NfL levels and lower limb neuropathy impairment scores. In other words, patients with higher NfL levels tended also to have more severe neuropathy symptoms.
Analyses comparing samples over time indicated that NfL levels tended to increase as neuropathy got worse and tended to decrease when neuropathy eased.
Among the two main patients’ groups, those with the p.Glu109Gln mutation showed a strong correlation between disease progression and increased [blood] NfL concentrations. … This correlation was less pronounced in patients with the p.Phe84Leu mutation.
Most of the patients in this study had one of two specific TTRÂ gene mutations: those known as p.Glu109Gln and p.Phe84Leu. The association between NfL levels and neuropathy impairment scores was notably stronger for those with the p.Glu109Gln mutation, the data showed.
Further, according to the researchers, there was a clear correlation between NfL levels and autonomic dysfunction severity in people with the p.Glu109Gln mutation. Meanwhile, there were minimal links between NfL and autonomic dysfunction for individuals with the p.Phe84Leu mutation.
“Among the two main patients’ groups, those with the p.Glu109Gln mutation showed a strong correlation between disease progression and increased [blood] NfL concentrations. … This correlation was less pronounced in patients with the p.Phe84Leu mutation,” the researchers wrote.
The team speculated that factors like differences in patient age might help explain the findings by mutation type. They stressed, however, that given the small number of patients in this study, further research is needed to validate the results.
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