Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease

Abstract

<h3>Background and objectives:</h3> Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities (WMA) and neurocognitive problems. Therefore, upcoming therapies also target the brain. Currently biomarkers reflecting CNS involvement are lacking. We aimed to study the association of Neurofilament Light and CNS involvement. <h3>Methods:</h3> To investigate the potential of NfL, we analysed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of &lt;1, 5 and 10 years, as well as around MRI scans. We compared the outcomes to levels in age and sex matched peers. Control samples were originally collected as part of routine blood work in children that underwent small surgeries and stored in the biobank of the Erasmus MC/ Sophia Children’s Hospital. <h3>Results:</h3> We analysed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patients) and compared these to outcomes of 71 matched peers. In the first year of age NfL levels in patients and controls were similar (10.3 vs. 11.0 pg/ml), but mixed linear model analysis showed a yearly increase of NfL of 6.0% in patients, compared to a decrease of 8.8% in controls (<i>p &lt; 0.001</i>). Higher NfL was associated with lower IQ scores (<i>p = 0.009</i>) and lower processing speed scores (<i>p = 0.001</i>). <h3>Discussion:</h3> We found significant differences in NfL levels between patients and controls, and a good association between NfL and cognition. NfL deserves further exploration as a biomarker for CNS involvement in patients with classic infantile Pompe disease.

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