title: Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism.
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.
authors: Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99202-2131, USA. k.vogel@wsu.edu
authors: Kara R
authors: KR
authors: Vogel
authors: Phillip L
authors: PL
authors: Pearl
authors: William H
authors: WH
authors: Theodore
authors: Robert C
authors: RC
authors: McCarter
authors: Cornelis
authors: C
authors: Jakobs
authors: K Michael
authors: KM
authors: Gibson
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000266:history / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D002986:Clinical Trials as Topic; D002658:Developmental Disabilities; D058788:GABA-B Receptor Antagonists / Q000627:therapeutic use; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency* / Q000266:history / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000172:deficiency / Q000378:metabolism*
chemical_list: D058788:GABA-B Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D050644:Succinate-Semialdehyde Dehydrogenase