Abstract
Neuronal ceroid lipofuscinosis type 1(CLN1 disease) is a rare autosomal recessive lysosomal storage disease caused by genetic defects of palmitoyl protein thioesterase-1(PPT1), leading to accumulation of lipofuscin granules in brain and progressive neurodegeneration. Psychomotor regression, seizures, loss of vision, and movement disorder begin in infancy and result in early death. Currently, no disease-modifying therapy is available. We report a 68-month-old boy with CLN1 treated on a compassionate use basis weekly for 26 months with a PPT1 enzyme fused to an anti-insulin receptor antibody (AGT-194), thereby enabling penetration of the blood-brain barrier (BBB). During treatment, no side effects were observed, while seizure frequency decreased, life quality improved, and the boy's general condition remained stable. This case documents for the first time that treatment of CLN1 is principally feasible by an intravenous BBB penetrating enzyme replacement therapy using PPT1 fused with the human insulin receptor. Monitoring of side effects raised no unacceptable or unexpected safety concerns.Observed improvement of life quality related to ameliorated epilepsy control raises hope that further robust clinical trials including patients in earlier stages of disease will show positive results.