Assessment of motor deterioration in a cynomolgus macaque with neuronal ceroid lipofuscinosis type 2 disease using two behavioral analyses.

Abstract

The classical late-infantile form of neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a fatal lysosomal disorder characterized by progressive motor decline and premature death. A CLN2 cynomolgus macaque (Macaca fascicularis) model closely replicates the late-stage clinical and pathological features of human CLN2. To evaluate motor deterioration in this model, we conducted two behavioral assessments-the CLN2 Macaque Clinical Rating Scale and the Apple test-from the pre-onset stage in one macaque. Hypokinesia was observed as the first symptom at 22 months of age, followed by a marked decline in forelimb movement from 27 months. These simple, non-invasive, and cost-effective tests are valuable tools for monitoring disease progression and may facilitate the future clinical evaluation of therapeutic strategies for CLN2.