PMID- 23581634
OWN - NLM
STAT- MEDLINE
DCOM- 20130729
LR  - 20231120
IS  - 1933-0715 (Electronic)
IS  - 1933-0707 (Linking)
VI  - 11
IP  - 6
DP  - 2013 Jun
TI  - Central nervous system stem cell transplantation for children with neuronal 
      ceroid lipofuscinosis.
PG  - 643-52
LID - 10.3171/2013.3.PEDS12397 [doi]
AB  - 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.
FAU - Selden, Nathan R
AU  - Selden NR
AD  - Department of Neurological Surgery, Oregon Health & Science University, 3303 SW 
      Bond Avenue, Portland, OR 97239, USA. seldenn@ohsu.edu
FAU - Al-Uzri, Amira
AU  - Al-Uzri A
FAU - Huhn, Stephen L
AU  - Huhn SL
FAU - Koch, Thomas K
AU  - Koch TK
FAU - Sikora, Darryn M
AU  - Sikora DM
FAU - Nguyen-Driver, Mina D
AU  - Nguyen-Driver MD
FAU - Guillaume, Daniel J
AU  - Guillaume DJ
FAU - Koh, Jeffrey L
AU  - Koh JL
FAU - Gultekin, Sakir H
AU  - Gultekin SH
FAU - Anderson, James C
AU  - Anderson JC
FAU - Vogel, Hannes
AU  - Vogel H
FAU - Sutcliffe, Trenna L
AU  - Sutcliffe TL
FAU - Jacobs, Yakop
AU  - Jacobs Y
FAU - Steiner, Robert D
AU  - Steiner RD
LA  - eng
SI  - ClinicalTrials.gov/NCT00337636
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20130412
PL  - United States
TA  - J Neurosurg Pediatr
JT  - Journal of neurosurgery. Pediatrics
JID - 101463759
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Tpp1 protein, mouse)
RN  - 0 (Tripeptidyl-Peptidase 1)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.4.14.9 (TPP1 protein, human)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Child
MH  - Child, Preschool
MH  - Dexamethasone/administration & dosage
MH  - Drug Administration Schedule
MH  - Feasibility Studies
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mycophenolic Acid/administration & dosage/analogs & derivatives
MH  - Neural Stem Cells/*transplantation
MH  - Neuronal Ceroid-Lipofuscinoses/*diagnosis/*surgery
MH  - Neurosurgical Procedures/*methods
MH  - Stem Cell Transplantation/*methods
MH  - Stereotaxic Techniques
MH  - Tacrolimus/administration & dosage
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - Tripeptidyl-Peptidase 1
EDAT- 2013/04/16 06:00
MHDA- 2013/07/31 06:00
CRDT- 2013/04/16 06:00
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2013/07/31 06:00 [medline]
AID - 10.3171/2013.3.PEDS12397 [doi]
PST - ppublish
SO  - J Neurosurg Pediatr. 2013 Jun;11(6):643-52. doi: 10.3171/2013.3.PEDS12397. Epub 
      2013 Apr 12.