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ABSTRACT
Introduction
The past decades have witnessed a remarkable improvement in the health of patients with Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, resulting from the availability of enzyme replacement and substrate reduction therapies. Especially in pediatric populations, early diagnosis and initiation of treatment is essential to achieving optimal outcomes.
Areas Covered
The authors review the literature pertaining to the effectiveness of currently available therapies and describe new pharmacotherapies under development, especially for young patients.
Expert opinion
For pediatric patients with non-neuronopathic Gaucher disease, there may be new therapeutic options on the horizon in the form of gene therapy or small molecule glucocerebrosidase chaperones. These have the potential to result in a cure for systemic disease manifestations and/or to reduce the cost and convenience of treatment. For children with neuronopathic Gaucher disease, the challenge of targeting therapy to the central nervous system is being explored through new modalities including brain-targeted gene therapy, in-utero therapy, brain-penetrant small molecule chaperones, and other methods that convey enzyme across the blood-brain barrier. Indeed, these are exciting times for both pediatric patients with Gaucher disease and those with other lysosomal storage disorders.
Declaration of interest
The Sidransky laboratory has received support from F.Hoffman-La Roche Ltd under a Cooperative Research and Development Agreement with the National Human Genome Research Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Abbreviations used
| GD:Gaucher disease | = | |
| LSD:lysosomal storage disorder | = | |
| GD1:type 1 Gaucher disease | = | |
| GD2:type 2 Gaucher disease | = | |
| GD3:type 3 Gaucher disease | = | |
| GCase:glucocerebrosidase | = | |
| ERT:enzyme replacement therapy | = | |
| SRT:substrate reduction therapy | = | |
| GluCer:glucosylceramide | = | |
| ICGC:International Collaborative Gaucher Group | = | |
| HRQoL:health-related quality of life | = | |
| NBS:newborn screening | = | |
| MS/MS:tandem mass spectrometry | = | |
| lyso-Gb1:glucosylsphingosine | = | |
| LC:liquid chromatography | = | |
| DBS:dried blood spot | = | |
| CHO:Chinese hamster ovary | = | |
| FDA:Food and Drug Administration | = | |
| BBB:blood-brain barrier | = | |
| HDACIs:histone deacetylase inhibitors | = | |
| HSP:heat shock protein | = | |
| IUERT:in utero ERT | = | |
| MPS7:Mucopolysaccharidosis type VII | = | |
| AAV:adeno-associated virus | = | |
| WT:wildtype | = | |
| IFeTIS:International Fetal Transplantation and Immunology Society | = | |
| IUGT:in utero-gene therapy | = | |
| SapC:saposin C | = | |
| DOPS:dioleoylphosphatidylserine | = | |
| iPSC:induced pluripotent stem cells | = |
Article highlights
During the past decades, efficacious new therapies have been developed for children with Gaucher disease which reverse or prevent many of the non-neurological manifestations.
However, the currently available therapies require life-long administration, are very costly, and do not cross the blood-brain-barrier.
Newborn screening programs, community carrier screening, and an increased awareness of the disorder have contributed to a more frequent identification of Gaucher disease in childhood, sometime before any disease manifestations are apparent.
Children with Gaucher disease should be monitored regularly, and if clinical manifestations develop, should be placed on Enzyme Replacement Therapy.
Glucosylsphingosine (lyso-Gb1) is a useful biomarker for evaluating the need for and response to treatment.
New therapies under development for Gaucher disease, including potentially the neuronopathic forms, are small molecule chaperones, gene therapy, in utero Enzyme Replacement Therapy and gene therapy, nanovesicle enzyme delivery, and brain-penetrant Substrate Reduction Therapy.
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