Alzheimer’s Disease Therapy, and the Effects of Genetic Polymorphisms on Its Efficacy and Safety

Abstract

Alzheimer’s disease (AD) continues to be a significant health burden worldwide as the global population is getting older and health care costs are escalating. AD is a heterogeneous condition having diverse phenotypes and genotypes, which is a major challenge in understanding disease etiopathogenesis. The difficulty in understanding the intricacies of the disease has led to recurrent failure of therapeutic agents in clinical trials resulting in an extremely slow and low success in the new drug discovery process for the AD. Currently approved agents for AD therapy are acetyl cholinesterase inhibitors (AchEIs) (donepezil, galantamine and rivastigmine) and n-methyl d-aspartate (NMDA) antagonist (memantine) that provide symptomatic relief only. However, extensive inter-individual variability in drug responsiveness is observed. ‘Pharmacogenomics’ which refers to how the genome of a patient might affect the treatment response to a drug, appears to play an important role in this inter-individual variability. By bringing pharmacogenomics profile of patients on AD therapy into consideration, it might be possible to gain maximum benefits from available treatments in terms of safety, therapeutic optimization and minimizing adverse effects. The purpose of this review is to provide better understanding of AD pathogenesis, challenges of current AD therapy and insight into the role of genetic polymorphism in drug response with focus on available therapeutic options in AD.