Does drug repurposing bridge the gaps in management of Parkinson’s disease? Unravelling the facts and fallacies

Abstract

Repurposing the existing drugs for the management of both common and rare diseases is increasingly appealing due to challenges such as high attrition rates, the economy, and the slow pace of discovering new drugs. Drug repurposing involves the utilization of existing medications to treat diseases for which they were not originally intended. Despite encountering scientific and economic challenges, the pharmaceutical industry is intrigued by the potential to uncover new indications for medications. Medication repurposing is applicable across different stages of drug development, with the greatest potential observed when the drug has undergone prior safety testing. In this review, strategies for repurposing drugs for Parkinson’s disease (PD) are outlined, a neurodegenerative disorder predominantly impacting dopaminergic neurons in the substantia nigra pars compacta region. PD is a debilitating neurodegenerative condition marked by an amalgam of motor and non-motor symptoms. Despite the availability of certain symptomatic treatments, particularly targeting motor symptoms, there remains a lack of established drugs capable of modifying the clinical course of PD, leading to its unchecked progression. Although standard drug discovery initiatives focusing on treatments that relieve diseases have yielded valuable understanding into the underlying mechanisms of PD, none of the numerous promising candidates identified in preclinical studies have successfully transitioned into clinically effective medications. Due to the substantial expenses associated with drug discovery endeavors, it is understandable that there has been a notable shift towards drug reprofiling strategies. Assessing the efficacy of an existing medication offers the additional advantage of circumventing the requirement for preclinical safety assessments and formulation enhancements, consequently streamlining the process and reducing both the duration of time and financial investments involved in bringing a treatment to clinical fruition. Furthermore, repurposed drugs may benefit from lower rates of failure, presenting an additional potential advantage. Various strategies for repurposing drugs are available to researchers in the field of PD. Some of these strategies have demonstrated effectiveness in identifying appropriate drugs for clinical trials, thereby providing validation for such strategies. This review provides an overview of the diverse strategies employed for drug reprofiling from approaches that place emphasis on single-gene transcriptional investigations to comprehensive epidemiological correlation analysis. Additionally, instances of previous or current research endeavors employing each strategy have been discussed. For the strategies that have not been yet implemented in PD research, their strategic efficacy is demonstrated using examples involving other disorders. In this review, we assess the safety and efficacy potential of prominent candidates repurposed as potential treatments for modifying the course of PD undergoing advanced clinical trials.