Central nervous system stem cell transplantation for children with neuronal ceroid lipofuscinosis

Nathan R. Selden, Amira Al-Uzri, Stephen L. Huhn, Thomas K. Koch, Darryn M. Sikora, Mina D. Nguyen-Driver, Daniel J. Guillaume, Jeffrey L. Koh, Sakir H. Gultekin, James C. Anderson, Hannes Vogel, Trenna L. Sutcliffe, Yakop Jacobs, Robert D. Steiner

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Object. Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model. Methods. HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression. Results. Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immunosuppression. The surgery, immunosuppression, and cell transplantation were well tolerated. Adverse events following transplantation were consistent with the underlying disease, and none were directly attributed to the donor cells. Observations regarding efficacy of the intervention were limited by the enrollment criteria requiring that patients be in advanced stages of disease. Conclusions. This study represents the first-in-human clinical trial involving transplantation of a purified population of human neural stem cells for a neurodegenerative disorder. The feasibility of this approach and absence of transplantation-related serious adverse events support further exploration of HuCNS-SC transplantation as a potential treatment for select subtypes of NCL, and possibly for other neurodegenerative disorders. Clinical trial registration no.: NCT00337636 (ClinicalTrials.gov).

Original languageEnglish (US)
Pages (from-to)643-652
Number of pages10
JournalJournal of Neurosurgery: Pediatrics
Issue number6
StatePublished - Jun 2013


  • Lysosomal storage disorders
  • Neural stem cells
  • Neurodegenerative disease
  • Neuronal ceroid lipofuscinosis
  • Neurosurgery
  • Pediatric
  • Transplantation


Dive into the research topics of 'Central nervous system stem cell transplantation for children with neuronal ceroid lipofuscinosis'. Together they form a unique fingerprint.

Cite this