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Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency

  • John M. SchreiberEmail author
  • Phillip L. Pearl
  • Irene Dustin
  • Edythe Wiggs
  • Emily Barrios
  • Eric M. Wassermann
  • K. Michael Gibson
  • William H. Theodore
Research Report
Part of the JIMD Reports book series (JIMD, volume 30)

Abstract

Aim: 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.

Method: Biomarkers including neuropsychological testing, TMS, and CSF metabolites were studied in a cohort of patients on and off three months’ taurine treatment.

Results: 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.

Interpretation: 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.

Keywords

Conditioning Stimulus Transcranial Magnetic Stimulation Motor Threshold First Dorsal Interosseous Cortical Silent Period 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Belluzzi O, Puopolo M, Benedusi M, Kratskin I (2004) Selective neuroinhibitory effects of taurine in slices of rat main olfactory bulb. Neuroscience 124:929–944CrossRefPubMedGoogle Scholar
  2. Bidri M, Choay P (2003) Taurine: a particular aminoacid with multiple functions. Ann Pharm Fr 61:385–391PubMedGoogle Scholar
  3. Buzzi A, Wu Y, Frantseva MV et al (2006) Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. Brain Res 1090:15–22CrossRefPubMedGoogle Scholar
  4. Chan CY, Sun HS, Shah SM, Agovic MS, Friedman E, Banerjee SP (2014) Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex. Eur J Pharmacol 728:167–175CrossRefPubMedGoogle Scholar
  5. Chen WQ, Jin H, Nguyen M et al (2001) Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons. J Neurosci Res 66:612–619CrossRefPubMedGoogle Scholar
  6. Cherubini E, Gaiarsa JL, Ben-Ari Y (1991) GABA: an excitatory transmitter in early postnatal life. Trends Neurosci 14:515–519CrossRefPubMedGoogle Scholar
  7. Gupta M, Greven R, Jansen EE et al (2002) Therapeutic intervention in mice deficient for succinate semialdehyde dehydrogenase (gamma-hydroxybutyric aciduria). J Pharmacol Exp Ther 302:180–187CrossRefPubMedGoogle Scholar
  8. Han NL, Haddrill JL, Lynch JW (2001) Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the beta-amino acid agonist, taurine. J Neurochem 79:636–647CrossRefPubMedGoogle Scholar
  9. Ilic TV, Meintzschel F, Cleff U, Ruge D, Kessler KR, Ziemann U (2002) Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity. J Physiol 545:153–167CrossRefPubMedPubMedCentralGoogle Scholar
  10. Inghilleri M, Berardelli A, Cruccu G, Manfredi M (1993) Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction. J Physiol 466:521–534PubMedPubMedCentralGoogle Scholar
  11. Jansen EE, Struys E, Jakobs C, Hager E, Snead OC, Gibson KM (2008) Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH) deficiency suggest a heightened excitatory state during development. BMC Dev Biol 8:112CrossRefPubMedPubMedCentralGoogle Scholar
  12. Junyent F, Utrera J, Romero R et al (2009) Prevention of epilepsy by taurine treatments in mice experimental model. J Neurosci Res 87:1500–1508CrossRefPubMedGoogle Scholar
  13. Kimiskidis VK, Papagiannopoulos S, Kazis DA et al (2006) Lorazepam-induced effects on silent period and corticomotor excitability. Exp Brain Res 173:603–611CrossRefPubMedGoogle Scholar
  14. Kok RM, Howells DW, van den Heuvel CC, Guerand WS, Thompson GN, Jakobs C (1993) Stable isotope dilution analysis of GABA in CSF using simple solvent extraction and electron-capture negative-ion mass fragmentography. J Inherit Metab Dis 16:508–512CrossRefPubMedGoogle Scholar
  15. McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173:86–93CrossRefPubMedGoogle Scholar
  16. Mody I, De Koninck Y, Otis TS, Soltesz I (1994) Bridging the cleft at GABA synapses in the brain. Trends Neurosci 17:517–525CrossRefPubMedGoogle Scholar
  17. Okamoto K, Kimura H, Sakai Y (1983) Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide). Brain Res 265:163–168CrossRefPubMedGoogle Scholar
  18. Pearl PL, Gibson KM, Acosta MT et al (2003a) Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. Neurology 60:1413–1417CrossRefPubMedGoogle Scholar
  19. Pearl PL, Novotny EJ, Acosta MT, Jakobs C, Gibson KM (2003b) Succinic semialdehyde dehydrogenase deficiency in children and adults. Ann Neurol 54(Suppl 6):S73–S80CrossRefPubMedGoogle Scholar
  20. Pearl PL, Gibson KM, Quezado Z et al (2009) Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. Neurology 73:423–429CrossRefPubMedPubMedCentralGoogle Scholar
  21. Pearl PL, Schreiber J, Theodore WH et al (2014) Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. Neurology 82:940–944CrossRefPubMedPubMedCentralGoogle Scholar
  22. Reis J, Cohen LG, Pearl PL et al (2012) GABAB-ergic motor cortex dysfunction in SSADH deficiency. Neurology 79:47–54CrossRefPubMedPubMedCentralGoogle Scholar
  23. Saronwala A, Tournay A, Gargus J (2008) Taurine treatment of succinate semialdehyde dehydrogenase (SSADH) deficiency reverses MRI-documented globus lesions and clinical syndrome. Conference Taurine treatment of succinate semialdehyde dehydrogenase (SSADH) deficiency reverses MRI-documented globus lesions and clinical syndrome., Phoenix AZ, 2008, 103.Google Scholar
  24. Tang ZQ, Lu YG, Chen L (2008) Developmental stability of taurine’s activation on glycine receptors in cultured neurons of rat auditory cortex. Neurosci Lett 430:54–59CrossRefPubMedGoogle Scholar
  25. Wu Y, Buzzi A, Frantseva M et al (2006) Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms. Ann Neurol 59:42–52CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • John M. Schreiber
    • 1
    Email author
  • Phillip L. Pearl
    • 2
  • Irene Dustin
    • 1
  • Edythe Wiggs
    • 1
  • Emily Barrios
    • 2
  • Eric M. Wassermann
    • 3
  • K. Michael Gibson
    • 4
  • William H. Theodore
    • 1
  1. 1.Clinical Epilepsy SectionBethesdaUSA
  2. 2.Department of Child NeurologyChildren’s National Medical Center (CNMC)Washington, DCUSA
  3. 3.Cognitive Neuroscience Section, NINDS, NIHBethesdaUSA
  4. 4.Experimental and Systems Pharmacology, Washington State University (WSU)SpokaneUSA

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