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Impact on GABA systems in monogenetic developmental CNS disorders: Clues to symptomatic treatment.
Journal article

Impact on GABA systems in monogenetic developmental CNS disorders: Clues to symptomatic treatment.

  • Benke D Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Neuroscience Center Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Drug Discovery Network Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: benke@pharma.uzh.ch.
  • Möhler H Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Neuroscience Center Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 10, 8023 Zurich, Switzerland. Electronic address: mohler@pharma.uzh.ch.
  • 2017-08-03
Published in:
  • Neuropharmacology. - 2018
Congenital nystagmus
Dravet's syndrome
Fragile X syndrome
GABA
Intellectual disability syndrome
NONO
Neurofibromatosis type 1
Rett syndrome
Succinic semialdehyde dehydrogenase deficiency
Animals
Humans
Neurodevelopmental Disorders
gamma-Aminobutyric Acid
English Animal studies of several single-gene disorders demonstrate that reversing the molecular signaling deficits can result in substantial symptomatic improvements in function. Focusing on the ratio of excitation to inhibition as a potential pathophysiological hallmark, seven single-gene developmental CNS disorders are reviewed which are characterized by a striking dysregulation of neuronal inhibition. Deficits in inhibition and excessive inhibition are found. The examples of developmental disorders encompass Neurofibromatosis type 1, Fragile X syndrome, Rett syndrome, Dravet syndrome including autism-like behavior, NONO-mutation-induced intellectual disability, Succinic semialdehyde dehydrogenase deficiency and Congenital nystagmus due to FRMD7 mutations. The phenotype/genotype correlations observed in animal models point to potential treatment options and will continue to inspire clinical research. Three drugs are presently in clinical trials: acamprosate and ganoxolon for Fragile X syndrome and SGS-742 for SSADH deficiency. This article is part of the "Special Issue Dedicated to Norman G. Bowery".
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/36726
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