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Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism
Author(s) -
Vogel Kara R.,
Pearl Phillip L.,
Theodore William H.,
McCarter Robert C.,
Jakobs Cornelis,
Gibson K. Michael
Publication year - 2013
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-012-9499-5
Subject(s) - vigabatrin , medicine , neurology , flumazenil , clinical trial , pharmacology , antagonist , epilepsy , anticonvulsant , psychiatry , receptor
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 GABA B receptor antagonist SGS742.