Surprising new tricks for old drugs
Investigators from the International Center for Biomedicine and the University of Chile, in collaboration with the Center for Bioinformatics of the Universidad de Talca, have discovered that two drugs, the benzimidazole derivatives lanzoprazole and astemizole, may be suitable for use as PET (positron emission tomography) radiotracers and enable imaging for the early detection of Alzheimer's Disease. The study is published in the current issue of the Journal of Alzheimer's Disease.
Lanzoprazole and astemizole specifically tag pathological oligomers of tau which form the core of neurofibrillary tangles (NFTs), a pathognomonic brain lesion in Alzheimer-s patients. Prof. Dr. R.B. Maccioni and Dr. Leonel Rojo, authors of the study commented, "Since neurofibrillary tangles are positively correlated with cognitive impairment, we propose that these drugs have great potential in PET neuroimaging for in vivo early detection of AD and in reducing the formation of NFTs. These studies, based on advanced proteomics and databases of molecular interactions, may help to find potential new drugs for early diagnosis and treatment of Alzheimer-s disease. The findings are the result of a long-standing research program supported by the Alzheimer-s Association-USA and Fondecyt, Chile to evaluate new drug candidates." Technological applications of this discovery are being developed with the collaboration of VentureL@b of the Universidad Adolfo Iba-ez.
Interestingly, lanzoprazole and astemizole, already approved for treatment of proton pump disorders and as an antihistamine respectively, specifically bind directly to aggregated variants of tau protein, paired helical filaments (PHFs) and NFTs in Alzheimer-s brains. Until now it has not been possible to detect these pathological brain structures in living Alzheimer-s patients. The only confirmation of the disease has been attained by postmortem neuropathological evaluation.