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VPA & MCT treatment in adults:

VPA & MCT treatment in adults: Teratogenicity – linked to inhibition of human histone deacetylase (HDAC) activity Hepatotoxicity – linked to inhibition of fatty acid β -oxidation in the mitochondrial matrix, increasing lipid droplet accumulation in hepatocytes Sedation.

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VPA & MCT treatment in adults:

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  1. VPA & MCT treatment in adults: • Teratogenicity – linked to inhibition of human histone deacetylase(HDAC) activity • Hepatotoxicity – linked to inhibition of fatty acid β-oxidation in the mitochondrial matrix, increasing lipid droplet accumulation in hepatocytes • Sedation

  2. Valnoctamide: a new 2nd generation VPA derivative • Decanoic Acid found to have new improved seizure control • Elevated in plasma of epilepsy patients on KD.

  3. Conclusions: • Compunds must show greater potency than current anti-epileptic drugs • Preferably in relation to refractory epilepsy • Possibility of a neuroprotective effect • Fewer side effects than those currently on the market • First study to demonstrate that nonanoic acid and octanoic acids branched at the 4th carbon can be effective seizure control treatments. Moreover, these two compounds demonstrate an improved dose-dependence for seizure control compared to VPA (in vivo and in vitro) • Nonanoic acid • 4-methyloctanoic • These compounds also showed no effect on HDAC inhibition, but in vivo work for birth defects must be explored

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