Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis.
The NCLs (neuronal ceroid lipofuscinoses) are the most common inherited paediatric neurodegenerative disorder. Although genetically distinct, NCLs can be broadly divided into two categories: one in which the mutation results in a defect in a transmembrane protein, and the other where the defect lies in a soluble lysosomal enzyme. A number of therapeutic approaches are applicable to the soluble lysosomal forms of NCL based on the phenomenon of cross-correction, whereby the ubiquitously expressed mannose 6-phosphate/IGF (insulin-like growth factor) II receptor provides an avenue for endocytosis, trafficking and lysosomal processing of extracellularly delivered enzyme. The present review discusses therapeutic utilization of cross-correction by enzyme-replacement therapy, gene therapy and stem cell therapy for the NCLs, along with an overview of the recent progress in translating these treatments into the clinic.
Pediatric Storage Disorders Laboratory, Department of Neuroscience and Centre for the Cellular Basis of Behaviour, MRC Centre for Neurodegeneration Research, James Black Centre, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK. andrew.2.wong@kcl.ac.uk
Andrew M S
AM
Wong
Ahad A
AA
Rahim
Simon N
SN
Waddington
Jonathan D
JD
Cooper
D000818:Animals; D002648:Child; D004705:Endocytosis / Q000502:physiology; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000145:classification / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation
D008565:Membrane Proteins; D018832:Molecular Chaperones; D017527:Receptor, IGF Type 2