Journal of Inherited Metabolic Disease

, Volume 32, Issue 3, pp 387–394

Consideration of gene therapy for paediatric neurotransmitter diseases

Symposium on Neurotransmitter Disorders

DOI: 10.1007/s10545-009-1054-7

Cite this article as:
Rotstein, M. & Kang, U.J. J Inherit Metab Dis (2009) 32: 387. doi:10.1007/s10545-009-1054-7

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.

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

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Neurology, Neurologic Institute of New YorkColumbia University Medical CenterNew YorkUSA
  2. 2.Department of NeurologyUniversity of ChicagoChicagoUSA
  3. 3.The University of Chicago Medical CenterChicagoUSA