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Consideration of gene therapy for paediatric neurotransmitter diseases

  • Symposium on Neurotransmitter Disorders
  • Published:
Journal of Inherited Metabolic Disease

Summary

The paediatric neurotransmitter diseases (PNDs) are a group of inborn errors of metabolism characterized by abnormalities of neurotransmitter synthesis or metabolism. Although some children may react favourably to neurotransmitter augmentation treatment, optimal response is not universal and other modes of treatment should be sought. The genes involved in many of the currently known monoamine PNDs have been utilized in pre-clinical and in phase I clinical trials in Parkinson disease (PD) and the basic principles could be applied to the therapy of PNDs with some modifications regarding the targeting and distribution of vectors. However, issues that go beyond neurotransmitter replacement are important considerations in PD and even more so in PNDs. Understanding the pathophysiology of PNDs including abnormal development resulting from the neurotransmitter deficiency will be critical for rational therapeutic approaches. Better animal models of PNDs are necessary to test gene therapy before clinical trials can be attempted.

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Abbreviations

AADC:

aromatic l-amino acid decarboxylase

AAV:

adeno-associated virus

BH4 :

tetrahydrobiopterin

GTPCH-I:

guanine triphosphate cyclohydrolase I

HSV:

herpes simplex viruses

LV:

lentiviruses

PD:

Parkinson disease

PND:

paediatric neurotransmitter disease

PTPS:

6-pyruvoyl-tetrahydropterin synthase

SR:

sepiapterin reductase

TH:

tyrosine hydroxylase

VMAT-2:

vesicular monoamine transporter

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Acknowledgement

M.R. is a recipient of a fellowship grant from the Paediatric Neurotransmitter Disease Association. U.J.K. was supported by NIH grant R01NS32080, Parkinson Disease Foundation, and American Parkinson Disease Association for the research described in the review. We thank Keith Hyland for helpful discussions.

The Symposium was supported in part by R13 NS 60363 from the NIH NINDS and Office of Rare Diseases (ORD), and the Johns Hopkins University School of Medicine.

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Authors and Affiliations

  1. Department of Neurology, Neurologic Institute of New York, Columbia University Medical Center, New York, New York, USA

    Michael Rotstein

  2. Department of Neurology, University of Chicago, Chicago, Illinois, USA

    Un Jung Kang

  3. The University of Chicago Medical Center, MC 2030, SBR J219, 5841 S. Maryland Avenue, Chicago, IL, 60637-1470, USA

    Un Jung Kang

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  1. Michael Rotstein
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  2. Un Jung Kang
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Correspondence to Un Jung Kang.

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Communicating editor: Michael Gibson

Competing interests: None declared

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Rotstein, M., Kang, U.J. Consideration of gene therapy for paediatric neurotransmitter diseases. J Inherit Metab Dis 32, 387–394 (2009). https://doi.org/10.1007/s10545-009-1054-7

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