Table 1.
Landmarks in SSADHD Research
| Year(s) | Achievement(s) | Citation(s) |
|---|---|---|
| 1981-1983 | Biochemical (GHB)/Enzymatic Identification of SSADHD | Jakobs et al 1981; Gibson et al 1983 |
| 1992 | Purification of Mammalian SSADHD | Chambliss and Gibson 1992 |
| 1993 | Prenatal Detection of SSADHD; Identification of CNS Enzyme Defect | Jakobs et al 1993; Chambliss et al 1993 |
| 1995-1998 | Molecular Cloning of ALDH5A1 Gene; Identification of Mutations | Chambliss et al 1995; 1998 |
| 1997 | Genotype/Phenotype Correlations in 23 Patients: Case Histories | Gibson et al 1997 |
| 2001-2002 | Development of Murine Knockout Mouse-Pharmacological Rescue | Hogema et al 2001; Gupta et al 2002 |
| 2003 | Compilation of 27 Disease-Associated Mutations in SSADHD | Akaboshi et al 2003 |
| 2004-2006 | Definition of KO Mouse Seizure Profile; GABABR/GABAAR Abnormalities |
Cortez et al 2004; Buzzi et al 2006; Wu et al 2006 |
| 2008 | Identification of Metabolic Disruptions in Embryonic KO Mice | Jansen et al 2008 |
| 2008 | Rescue of KO Mice with the Ketogenic Diet | Nylen et al 2008 |
| 2009 | Human GABAAR Dysfunction using 11C-Flumazenil Binding | Pearl et al 2009 |
| 2009 | Crystal Structure of Human SSADH; “Dynamic Catalytic Loop” | Kim et al 2009 |
| 2009 | Efficacy of SGS-742 (GABABR antagonist) in KO Mouse | Pearl et al 2011 |
| 2012 | Human GABABR Dysfunction using Transcranial Magnetic Stimulation | Reis et al 2012 |
| 2014 | Clinical Trial of Taurine Intervention in SSADHD (completed)a | Pearl et al 2014a |
| 2014 | Clinical Trial of SGS-742 Intervention in SSADHD (ongoing) | (unpublished) |
| 2014, 2015 | Identification of GABA Role in Autophagy; Rapalog Therapeutics | Lakhani et al 2014; Vogel et al 2015 |
Legend to Table: Abbreviations employed: GHB, gamma-hydroxybutyric acid; CNS, central nervous system; GABAAR, GABAA receptor; GABABR, GABAB receptor; ALDH5A1=aldehyde dehydrogenase 5a1=succinic semialdehyde dehydrogenase; KO=knockout.
a
Taurine is a non-physiological amino acid with pleiotropic GABAergic roles, and was effective in rescuing early lethality in KO mice (Gupta et al 2002).