GENETICS IN MEDICINE | NOVEMBER 26, 2020

Dang Do AN, Sinaii N, Masvekar RR, Baker EH, Thurm AE, Soldatos AG, Bianconi SE, Bielekova B and Porter FD.

Genet Med (2020).

DOI: https://doi.org/10.1038/s41436-020-01035-3

ABSTRACT

PURPOSE

CLN3 disease is a neurodegenerative disorder with onset in childhood. It affects multiple functions at different developmental stages. Incomplete understanding of the pathophysiology hampers identification of cell and tissue biochemical compounds reflective of the disease process. As treatment approaches are being explored, more sensitive, objective, quantifiable, and clinically relevant biomarkers are needed.

METHODS

We collected prospective biosamples from 21 phenotyped individuals with CLN3. We measured neurofilament light chain (NEFL) levels, a marker of neuronal damage, in cross-sectional CSF and serum samples from individuals with CLN3 and in pediatric non-CLN3 controls using two different assays.

RESULTS

Cerebrospinal fluid (CSF) and serum NEFL levels are significantly higher in CLN3 (CSF: 2096 ± 1202; serum: 29.0 ± 18.0 pg/mL) versus similarly aged non-CLN3 (CSF: 345 ± 610; serum: 6.7 ± 3.2 pg/mL) samples. NEFL levels correlate with Unified Batten Disease Rating Scale and adaptive behavior composite scores, and magnetic resonance (MR) spectroscopy markers. NEFL levels from CSF and serum are strongly correlated (rp = 0.83; p < 0.0001).

CONCLUSION

CSF and serum NEFL levels increase in multiple neurologic conditions. Here, we show that CSF and serum NEFL levels also increase in CLN3 (versus non-CLN3) and correlate with other disease-relevant measures. These findings suggest NEFL as a relevant and feasible biomarker for applications in CLN3 clinical trials and management.