Pre-clinical development of an enzyme replacement therapy (CPI-601) for CLN1 Batten disease: process development, stability and uptake studies in different species

treatment increased myelination in dorsal root ganglion (DRG) explants, as evidenced by a rise in myelin segments (17.67 3.48 vs. 72.67 4.37; p < 0.05, n = 3).In vivo, 2-PMPA accelerated remyelination in a sciatic nerve crush injury model in aged mice, as indicated by a reduced g-ratio (0.90 0.01 vs. 0.73 0.05; p < 0.05, n = 3) and a higher proportion of remyelinated axons (28.1 2.1 vs. 82.5 7.2%; p < 0.05, n = 3).Dendrimer-conjugated 2-PMPA, targeting GCPII inhibition specifically in macrophages and Schwann cells, further validated this approach.Electrophysiological assessments revealed a significant reduction in compound muscle action potential (CMAP) latency after 10 weeks of Dendrimer-2-PMPA treatment on aged PNI mice (4.04 0.11 vs. 3.23 0.13 ms; p < 0.01, n = 5).These findings highlight GCPII inhibition as a promising therapeutic strategy to enhance remyelination in aging populations with compromised recovery after PNI.