Testing the mettle of PBT2 for Alzheimer's disease

摘要

Copper, zinc, and iron have long been known to promote the aggregation of amyloid beta (Ap). Until recently, this effect of metal ions was viewed as more of a laboratory curiosity than a premise for treating Alzheimer's disease (AD). After all, Cu~(2+) and Zn~(2+) have important roles in synaptic function and as co-factors for Abeta-degrading enzymes. Consequently, decreasing the concentrations of these ions in the brain is not a viable option to reduce Abeta accumulation in patients with AD. In this issue of The Lancet Neurology, Lannsfeld and colleagues report the results of a phase II clinical trial of PBT2, an orally administered quinoline compound that alters the interaction between Abeta and metal ions without lowering their concentration. The results of laboratory studies indicate that PBT2 not only reduces amyloid aggregation and toxicity but also can increase the availability of divalent metal ions to neurons.The results of this phase II study suggest that this rather inventive approach to anti-Abeta therapy might hold promise for the treatment of AD.