Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Kara R Vogel; Phillip L Pearl; William H Theodore; Robert C McCarter; Cornelis Jakobs; K. Michael Gibson

doi:10.1007/s10545-012-9499-5

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Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Journal article

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Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Kara R Vogel, Phillip L Pearl, William H Theodore, Robert C McCarter, Cornelis Jakobs and K. Michael Gibson

Journal of inherited metabolic disease, Vol.36(3), pp.401-410

05/2013

DOI: https://doi.org/10.1007/s10545-012-9499-5

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https://hdl.handle.net/2376/110445

PMCID: PMC4349389

PMID: 22739941

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Abstract

This review summarizes a presentation made at the retirement Symposium of Prof. Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L‐cycloserine, the GHB receptor antagonist NCS‐382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11 C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open‐label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742.

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Title: Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism
Creators: Kara R Vogel - Washington State University
Phillip L Pearl - Children's National Medical Center and the George Washington University School of Medicine
William H Theodore - National Institutes of Health
Robert C McCarter - Children's National Medical Center and the George Washington University School of Medicine
Cornelis Jakobs - VU University Medical Center
K. Michael Gibson - Washington State University
Publication Details: Journal of inherited metabolic disease, Vol.36(3), pp.401-410
Academic Unit: Pharmacotherapy, Department of
Publisher: Springer Netherlands; Dordrecht
Number of pages: 10
Grant note: Pediatric Neurotransmitter Disease Association NIH (HD 58553)
Identifiers: 99900547115901842
Language: English
Resource Type: Journal article