Biomarkers are an integral part of the development of new therapies for neuronal ceroid lipofuscinoses (NCLs). The aim of this collaboration project was a multi-disciplinary in-depth approach to identify new biomarkers that mimic CNS damage and to validate these biomarkers as efficacy readout for novel experimental therapies. Currently, there remains a notable lack of validated biomarkers for disease progression and monitoring in NCLs.
Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAP) levels were tested in 26 serum samples of a total of 24 patients with different NCL forms using the Simoa® method. Levels were correlated with patients‘ age and disease stage. Disease stages were determined using various disease specific clinical scores such as the Hamburg iCRS scale for infantile CLN1, the Hamburg LINCL for late-infantile CLN2 and the Unified Batten Disease rating Scale (UBDRS) for CLN3 patients.
NfL levels were significantly increased above control levels in all serum samples with median NfL levels of 48.84pg/ml (IQR 38.2pg/ml) for CLN1, of 189.21pg/ml (IQR 116.14pg/ml) for CLN2, of 21.12pg/ml (IQR 16.28pg/ml) for CLN3 and of 102.77pg/ml (IQR 245.09pg/ml) for CLN7 patients. GFAP levels were not significantly increased above healthy controls but showed a wider range especially in CLN1 and CLN2 patients with levels ranging from 320.16pg/ml to 1853.48pg/ml in infantile CLN1 and from 259.08pg/ml to 987.20pg/ml in CLN2 patients.
CLN3 patients (n=16 samples) showed a moderate correlation of NfL levels with the physical assessment cumulative of the UBDRS (Spearman Correlation coefficient 0.573,p=0.02) as well as the cumulative Capability Assessment (Spearman Correlation coefficient 0.523,p=0.038), whereas GFAP did not correlate to any subpart of the UBDRS.
These results show that NfL has potential as a biomarker for various forms of NCL, whereas GFAP does not. These first results will be further validated prospectively in larger patient cohorts in an ongoing project.