Repurposed Drugs as Potential Therapeutic Candidates for the Management of Alzheimer's Disease.

Abstract

Drug repurposing is an innovative approach as it provides new indications for already approved and established drugs. Due to high failure rates and cost involved in traditional drug development procedures, many pharmaceutical companies are primarily focusing on drug repurposing strategy. In Alzheimer disease (AD), existing therapeutic agents only provide symptomatic benefits and does not play a role in disease modification, therefore, an alternative strategy of repurposing can be used to inhibit neurodegeneracy process and other pathological complications. This review discusses the beneficial effects of available licensed drug compounds which can be used as repurposed drugs for the treatment of AD. Moreover, it includes a brief overview of current treatment strategies, including therapies based on nanotechnology and their limitations. We attempted an organized scan of peer-reviewed research articles pertinent to licensed drugs that showed beneficial effects in Alzheimer's pathology. Our search includes in vitro studies, epidemiological data and clinical trials. In fact, we have collected, scrutinized, analyzed and discussed all the data that suggested the plausible application of repurposed drugs for the treatment of AD. Cholinesterase inhibitors and N-methyl-D-Aspartate receptor antagonist are available options to improve the cognitive functions of Alzheimer's patients. These drugs only help in balancing disturbed level of neurotransmitters and are not helpful in disease modification. On the other hand, the nanotechnological based approach has promised to solve some challenges, but has certain limitations such as biocompatibility issues, therefore, it requires an extensive amount of research work. As our main emphasis was on repurposed drugs, we have performed an extensive review of articles to identify compounds that have been approved by the United States Food and Drug Administration for the treatment of diseases other than Alzheimer's but might have an impact on AD modification based on clinical evidences. Amyloid clearance, tau pathology and anti-inflammatory mechanisms are potential factors that are taken into consideration for disease modification. In addition, the role of bioinformatics and in silico drug repurposing strategy is crucial in the field of drug research, and plays a significant role in the identification of potential repurposed drugs. Thus, we have also mentioned several drug repurposing computational tools that are robust and can predict reliable results based on available gene expression data. The major advantage of repurposing strategy is the identification of drug compounds with known mechanism of action, toxicology information and pharmacodynamics profiles; hence, less time is required for devising AD modification treatment. There are some issues as well with this method, which can be resolved by extending our research in this domain. AD is incurable, and there is an urgent need to find new treatments, as it is affecting the number of families and society overall. The drug repurposing approach is gaining attention in the pharmaceutical world, as it can substantially reduce the time and cost required to advance any treatment to the stage of clinical trials..