Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease

Neurology. 2006 Feb 28;66(4):602-4. doi: 10.1212/01.WNL.0000198762.41312.E1.

Abstract

LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / pharmacokinetics
  • Alanine / therapeutic use
  • Alzheimer Disease / drug therapy*
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Azepines / pharmacokinetics
  • Azepines / therapeutic use*
  • Endopeptidases / metabolism*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Placebos

Substances

  • Azepines
  • Enzyme Inhibitors
  • N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide
  • Placebos
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Alanine