Hematopoietic stem cell transplantation in infantile neuronal ceroid lipofuscinosis

Objective: To study the effect of allogeneic hematopoietic stem cell transp lantation (SCT) on the clinical course of infantile neuronal ceroid lipofus cinosis (INCL), a lysosomal storage disease. Background: INCL is a progress ive encephalopathy with severe neuronal loss, especially in the cerebral an d cerebellar cortex and retina. Autofluorescent lipopigments constitute the typical storage material in INCL. The disease is caused by recessive mutat ions in the palmitoyl protein thioesterase 1 (PPT1) gene. PPT1 is a depalmi toylating enzyme, which is transported to lysosomes through the mannose-6-p hosphate receptor-mediated pathway, and participates in the lysosomal degra dation of fatty acylated proteins. Methods: Three patients with INCL receiv ed transplants and were followed up after SCT at the Hospital for Children and Adolescents at the University of Helsinki. The first patient rejected t he first graft at the age of 7 months and had mild symptoms of INCL at the second transplantation at 11 months. The two other patients were asymptomat ic when they received their transplants at the age of 4 months. Results: PP T1 enzyme activity was normalized in peripheral leukocytes, but remained lo w in the CSF and resulted only in a mild and transient amelioration of the classic INCL. All patients who received transplants developed INCL by the a ge of 2 or 3 years. Conclusions: More experimental animal and cell culture studies are needed to determine the in vivo function of PPT1. SCT currently cannot be recommended as therapy for INCL.