Identification of Plasma Growth Factors and Cytokines as Diagnostic Biomarkers for the Lafora Form of Progressive Myoclonus Epilepsy

Abstract

Lafora disease; Diagnostic biomarker; Plasma samples

Malaltia de Lafora; Biomarcador diagnòstic; Mostres de plasma

Enfermedad de Lafora; Biomarcador diagnóstico; Muestras de plasma

Lafora progressive myoclonus epilepsy (LD, OMIM#254780, ORPHA:501) is an ultra-rare and severe autosomal recessive neurological disorder that typically manifests in early adolescence. It is characterized by the accumulation of insoluble forms of aberrant glycogen in the brain and peripheral tissues. Given the urgent need for reliable tools to monitor disease progression, we aimed to identify reliable biomarkers in minimally invasive fluids, which could also provide valuable insights into the natural history of the disease. Plasma-EDTA samples from eleven LD patients and healthy controls were analyzed to identify potential biomarkers of LD using a high-throughput assay. The findings were subsequently validated using specific enzyme-linked immunosorbent assays (ELISAs). Eleven cytokines and growth factors were identified to be significantly reduced in LD patient samples compared to healthy controls. Among these, four mediators [platelet-derived growth factor subunit B (PDGF-BB), epidermal growth factor (EGF), brain derived growth factor (BDNF), and macrophage migration inhibitory factor (MIF)] exhibited the greatest fold change between the groups and were further validated. Given the minimally invasive nature of plasma sampling and the straightforward quantification via ELISA assays, these biomarkers hold strong promise for rapid translation to the clinic, potentially enhancing early diagnosis and longitudinal disease monitoring in LD patients.

This work was supported by grants from the Spanish Ministry of Science and Innovation (PID2023-148103OB-I00), la Fundació La Marató TV3 (202032), CIBERER (ACCI2020 and ACCI2023-03-742), and the Prometeo program from Generalitat Valenciana (CIPROM2022/42) to P.S.