Journal article
Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency
JIMD reports, Vol.30, pp.81-87
2016
Handle:
https://hdl.handle.net/2376/105102
PMCID: PMC5110443
PMID: 27338723
Abstract
We tested the hypothesis that patients with succinic semialdehyde dehydrogenase (SSADH) deficiency on taurine would have decreased cortical excitability as measured by transcranial magnetic stimulation (TMS) and improved cognition, due to taurine's partial GABA(A and B) receptor agonist effects and rescue in the null mouse model from status epilepticus and premature lethality.
Biomarkers including neuropsychological testing, TMS, and CSF metabolites were studied in a cohort of patients on and off three months' taurine treatment.
Seven patients (5M/2F; age range 12-33 years) were enrolled in this open-label crossover study. Baseline average full-scale IQ (FSIQ) was 44.1 (range 34-55). Of six who returned at 6-month follow-up, five completed cognitive testing (3M/2F) on therapy; average FSIQ = 43.4 (range 33-51). CSF biomarkers (n = 4 subjects) revealed elevation in taurine levels but no change in free or total GABA. Baseline cortical excitability measured with TMS agreed with previous findings in this population, with a short cortical silent period and lack of long-interval intracortical inhibition. Patients on taurine showed a decrease in cortical silent period and short-interval intracortical inhibition compared to their off taurine study.
TMS demonstrated decreased inhibition in patients on taurine, in contrast to the study hypothesis, but consistent with its failure to produce clinical or cognitive improvement. TMS may be a useful biomarker for therapy in pediatric neurotransmitter disorders.
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Details
- Title
- Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency
- Creators
- John M Schreiber - Clinical Epilepsy Section, Bethesda, MD, USA. jschreib@childrensnational.orgPhillip L Pearl - Department of Child Neurology, Children's National Medical Center (CNMC), Washington, DC, USAIrene Dustin - Clinical Epilepsy Section, Bethesda, MD, USAEdythe Wiggs - Clinical Epilepsy Section, Bethesda, MD, USAEmily Barrios - Department of Child Neurology, Children's National Medical Center (CNMC), Washington, DC, USAEric M Wassermann - Cognitive Neuroscience Section, NINDS, NIH, Bethesda, MD, USAK Michael Gibson - Experimental and Systems Pharmacology, Washington State University (WSU), Spokane, WA, USAWilliam H Theodore - Clinical Epilepsy Section, Bethesda, MD, USA
- Publication Details
- JIMD reports, Vol.30, pp.81-87
- Academic Unit
- Pharmacotherapy, Department of
- Publisher
- United States
- Grant note
- U54 HD090255 / NICHD NIH HHS
- Identifiers
- 99900546955501842
- Language
- English
- Resource Type
- Journal article