Therapeutics

PBT2

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Overview

Name: PBT2
Therapy Type: Small Molecule
Target Type: APP and Amyloid-Related (timeline), Metals
Condition(s): Alzheimer's Disease, Huntington's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2), Huntington's Disease (Phase 2)
Company: Prana Biotechnology Limited

Background

PBT2 is a second-generation metal-protein attenuating compound (MPAC). It does not act as a metal chelator but rather as an ionophore that facilitates translocation of copper and zinc.  It is thought that by facilitating the translocation of copper and zinc into the cell, PBT2 reduces extracellular levels of these metals and thereby reduces metal-mediated Aβ aggregation (Lannfelt et al., 2008; Crouch et al., 2011). 

Findings

The association of metal ions (copper, zinc, and iron) with Aβ promotes its aggregation (Bush et al., 1994). 

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References

Paper Citations

  1. . Modulation of A beta adhesiveness and secretase site cleavage by zinc. J Biol Chem. 1994 Apr 22;269(16):12152-8. PubMed.
  2. . Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2008 Sep;7(9):779-86. PubMed.
  3. . The Alzheimer's therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity. J Neurochem. 2011 Oct;119(1):220-30. PubMed.

Further Reading

Papers

  1. . Metal protein attenuating compounds for the treatment of Alzheimer's dementia. Cochrane Database Syst Rev. 2014 Feb 21;2:CD005380. PubMed.