Abstract
BACKGROUND AND OBJECTIVES: 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 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 (NfL) and CNS involvement. METHODS: To investigate the potential of NfL, we analyzed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of <1, 5, and 10 years, as well as around MRI scans. We compared the outcomes with levels in age- and sex-matched peers. Control samples were originally collected as part of routine blood work in children who underwent small surgeries and stored in the biobank of the Erasmus MC/Sophia Children's Hospital. RESULTS: We analyzed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patient) and compared these with 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 with a decrease of 8.8% in controls (p < 0.001). Higher NfL was associated with lower IQ scores (p = 0.009) and lower processing speed scores (p = 0.001). DISCUSSION: 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.
| Original language | English |
|---|---|
| Pages (from-to) | e594-e601 |
| Journal | Neurology |
| Volume | 101 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 8 Aug 2023 |
Bibliographical note
Funding Information:Research on Pompe disease at the Erasmus MC is financially supported by the Prinses Beatrix Spierfonds (project number W.TR19-02), For Wis(h)dom Foundation, LSH-TKI (project number LSHM16008), and Stichting Ziekte van Pompe. Several of the authors of this publication are members of the European Pompe Consortium (EPOC), European Reference Networks for Hereditary Metabolic Disorders (Metab-ERN) and Rare Neuromuscular Diseases (EURO-NMD), and/or Netherlands Neuromuscular Center (NL-NMD). In addition, research by C.E. Teunissen was supported by the European Commission (Marie Curie International Training Network, grant agreement no. 860197 [MIRIADE] and JPND), Health Holland, Dutch Research Council (ZonMW), Alzheimer's Drug Discovery Foundation, Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer's Association.
Funding Information:
The Article Processing Charge was funded by the authors.
Funding Information:
Research on Pompe disease at the Erasmus MC is financially supported by the Prinses Beatrix Spierfonds (project number W.TR19-02), For Wis(h)dom Foundation, LSH-TKI (project number LSHM16008), and Stichting Ziekte van Pompe. Several of the authors of this publication are members of the European Pompe Consortium (EPOC), European Reference Networks for Hereditary Metabolic Disorders (Metab-ERN) and Rare Neuromuscular Diseases (EURO-NMD), and/or Netherlands Neuromuscular Center (NL-NMD). In addition, research by C.E. Teunissen was supported by the European Commission (Marie Curie International Training Network, grant agreement no. 860197 [MIRIADE] and JPND), Health Holland, Dutch Research Council (ZonMW), Alzheimer's Drug Discovery Foundation, Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer's Association.
Publisher Copyright:
Copyright © 2023 The Author(s).