Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm

EBioMedicine

Jerzy Leszek¹  Urszula Wojda²  Andrew Want²  Wioleta Grabowska-Pyrzewicz² 

[1] Department of Psychiatry, Wroclaw Medical University, Wybrzeże Pasteura 10, 50-367 Wroclaw, Poland;Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland;

关键词: Neurodegeneration;    Alzheimer's disease;    therapy;    gene therapy;    RNA therapy;    antisense oligonucleotide;   

DOI  :  

来源: DOAJ

【 摘 要 】

Alzheimer's disease (AD) represents a particular therapeutic challenge because its aetiology is very complex, with dynamic progression from preclinical to clinical stages. Several potential therapeutic targets and strategies were tested for AD, in over 2000 clinical trials, but no disease-modifying therapy exists. This failure indicates that AD, as a multifactorial disease, may require multi-targeted approaches and the delivery of therapeutic molecules to the right place and at the right disease stage. Opportunities to meet the challenges of AD therapy appear to come from recent progress in knowledge and methodological advances in the design, synthesis, and targeting of brain mRNA and microRNA with synthetic antisense oligonucleotides (ASOs). Several types of ASOs allow the utilisation of different mechanisms of posttranscriptional regulation and offer enhanced effects over alternative therapeutics. This article reviews ASO-based approaches and targets in preclinical and clinical trials for AD, and presents the future perspective on ASO therapies for AD.

【 授权许可】

Unknown