Trials, Tech, and Triumphs of Drug Repurposing

Drug repurposing, also known as drug repositioning, can be defined as a process of identifying pharmacological indications from existing approved drugs and the application of newly developed drugs to the treatment of diseases other than the drug’s intended for therapeutic uses. Given the high attrition rates, substantial costs, and slow pace of new drug discovery and development, the repurposing of existing drugs is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. The pharmaceutical industry has long used internal networking and disease-related phenotypic assays to explore the potential of new drugs in different disease areas. Drug repositioning is not a new concept. Many medications, whether in development or on the market, have been repurposed for new indications based on clinical observations (e.g., sildenafil) or improved knowledge of their mechanism of action (e.g., thalidomide). The initial drug repurposing was mainly through serendipity. Later, with time and advancements in technology, scientists started using various methods, like in vivo and in vitro, to repurpose drugs. There are two approaches for repurposing. The first approach, the traditional method, is experiment-based, while the other, the most recent one, is in silico-based approach. The experiment-based method is also called the activity-based method, which mainly focuses on screening of original drugs for unused pharmacological signs based on experimental measures. It includes in vitro or in vivo model building without the need for any basic data on the target protein. In contrast, the in silico method involves the use of bioinformatics, computational biology, and modern AI tools to screen huge databases of drug and chemical libraries. This method is time and labor-effective and reduces the risk of failure; this is the reason why it gained popularity and success in drug delivery programs. Thus, in this paper, we will delve into the developmental progression of successful drug repurposing over time.

Drug repurposing is a method that is used to explore alternative therapeutic usages of compounds that are abandoned during the research period and also prolong the use of pharmaceuticals currently in use. Drug repurposing process is considered to be a critical approach, especially in the case of rare genetic disorders, where the conventional drug development process is costly and time-consuming, considering the uncommon nature of the diseases. Although drug repurposing is not a new concept, it has gained popularity over the past decade due to the substantial benefits it provides to the pharmaceutical industry. From 1991 to 2000, there was a substantial decline in the rates occurring during Phase II studies, which examined the effectiveness and safety criteria of medication candidates. Therefore, many tactics such as collaborations, acquisitions, and the use of modern technologies were used to optimise the drug development process, but had very little impact. Given these interferences, repurposing of drugs looks like a potential way to overcome these barriers during the drug development process. Drug repurposing can be used to re-examine promoted drugs, inhibited drugs, and drug contenders that were dropped during the clinical phase for various reasons. In recent times, computational methods have played a crucial part in repurposing drugs, as they provide researchers with methods and tools for incorporating data available on diseases, targets, and drugs, which can later be used to shed light on previously undiscovered processes. Drug repurposing has had a major impact on neglected diseases as effective treatments were not available in the past.

Sometimes, due to some genetic mutations in pathogens and other circumstances, they become resistant to the existing drugs and become virulent to a certain kind of species, or specifically, humans. Then, during that time, to fight against that mutant pathogen, we need to develop another effective drug asap, which is nearly impossible. Because designing a drug requires a significant investment and a long time as a set of trials is conducted over a long period. This is the reason why fatal cases will be outnumbered. For this reason, scientists actually discovered another approach to using existing drugs to cure a novel disease. One drug could be used not only to treat one disease but also to cure many diseases when combined with other drugs. This chapter covers many methods for repurposing medications. There are many methods for testing drugs' ability to cure diseases and their effects in cell lines and animal models, such as phenotypic screening and target-based approaches. Molecular docking can predict the drug ligand or drug protein interaction, which actually helps us understand the pharmacological activity of the drug and pharmacodynamics of the drug, and gives us a way of treating a disease related to it. Besides, there are many techniques by which we can assess the effects of a drug not only on a particular disease but also on other diseases. 

Frontotemporal dementia is a type of frontotemporal degeneration disease that includes various forms of dementia, characterized by a considerable disintegration of the front and side pieces of grey matter in the brain in both sexes. Most of the people suffering from this disease demonstrate a gradual change in their behaviour or language disorders. Signs and symptoms often have their onset in the late adult years, usually between the ages of 45 and 65, but may occur before or after this. There are currently no effective or approved symptomatic treatments for FTD, although some off-label medications and behavioural methods may be used. Frontotemporal dementia (FTD) is a striking illness since it is a type of dementia that has no cure. This nature of the impairment exists as a consequence of brain deterioration. It results in a kind of brain lesion that cannot heal. As there is no cure or drug available for FTD, research is ongoing. A drug repurposing strategy can accelerate drug development and reduce costs and timeframes. Recent advancements in the understanding of FTD’s pathophysiology, including protein aggregation, neuroinflammation, and synaptic dysfunction, have opened avenues for repurposing drugs initially developed for other conditions such as neuropsychiatric disorders, metabolic diseases, and cancer. Within the realm of FTD, various compounds that include antipsychotics, antidepressants, and kinase inhibitors possess potential therapeutic effects, and research works are ongoing to evluate them . Identifying multiple compounds as potential FTD targets may disrupt a few pathways that contribute to the range leading to tau protein aggregation, as well as TDP-43 pathology, in preclinical and clinical experiments.

The past century has been marked by intense efforts, both in the pharmaceutical industry and academia, to provide new treatments to individuals suffering from various RAIDs, which often occur by ‘borrowing’ treatments that have been previously used in one RAID or in some completely different disease, a process called drug repurposing. In spite of typical clinical symptoms and immunological dysregulation, the disease pathophysiology and phenotype differ widely among RAIDs, and a lack of information about their causation has made the repurposing of medications for RAIDs difficult. Nonetheless, the last century has been marked by many 'waves' of repurposing. Earlier drug repurposing happened in academia and was motivated by incidental findings or apparent disease similarities, which were often affected by the popularity and availability of scientific therapeutic classes. Since the late 19th century, the majority of biological medicines have been created for one or several RAIDs and subsequently evaluated in combination, with variable degrees of success. Over the last two decades, data-driven drug repurposing has been witnessed, which is distinguished by signature-based techniques that depend on genetics and molecular biology. In addition, many data-driven strategies use computational modelling and machine learning to combine various data sources. These repurposing phases have jointly led to breakthroughs in the treatment of various RAIDs. 

Among the various kinds of neurodegenerative diseases that affect individuals worldwide, Parkinson's disease (PD) is one of the most common that affects an estimated 1-2 percent of individuals over the age of 65 all across the globe. The gradual degeneration of dopaminergic neurons within the substantia nigra pars compacta is a signature characteristic of PD, resulting in a deficiency of dopamine, a neurotransmitter vital for regulating motor functions and coordinating movements. While scientists are yet to have a complete picture of the cause of the deterioration of the neurons due to PD, it has been hypothesized that genetic mutation, amyloid deposition, environmental toxins, and inflammation are among the factors responsible, making the disease complex and multifaceted. Despite PD being such a common neurodegenerative disease, there is currently no available cure for it. A drug that functions as a one-size-fits-all is a challenging task, given the multifaceted nature of the disease, as well as the cost and risks associated with the discovery of a novel drug, which makes pharmaceutical companies hesitant to invest. This makes repurposing already existing and approved drugs for mitigating symptoms and slowing down the progression of PD for individuals suffering from the disease all the more important, with a handful of repurposed drugs already in the market and others currently being in the pipeline. We take a look at the pathogenesis of the disease and discuss drugs that are either approved or currently in clinical trials, alongside future prospects for repurposing drugs against PD.

 With an escalating increase in ailments and drug treatment failures, there has arisen a pressing need for the pharmaceutical industry to come up with effective drugs faster than ever before. Traditional drug development entails extensive research, augmentation, screening, and rigorous clinical trials, all of which are resourceintensive. An alternative approach has therefore been adopted in recent times, known as drug repurposing. Repurposing drugs involves finding new uses for an existing medication and demonstrating its effectiveness in treating diseases different from its prior indications. As recently as 2020, drug repurposing has found its place in the scientific community in light of the COVID-19 pandemic. Salient features of drug repurposing include reutilization of current and even household drugs, thereby expediting clinical trials and research time. The aegis of drug repurposing has stretched its branches to two ubiquitous drugs: Aspirin and Metformin. Customarily consumed aspirin, an over-the-counter drug, is conventionally used to treat a range of bodily pains and as an antiplatelet. Nevertheless, it has been found that aspirin can be repurposed to prevent cancer metastasis and revitalize the immune response. On the other hand, metformin, known for its hypoglycaemic activity, is a go-to choice for patients with Type II Diabetes. Over time, it has been observed that, when used as an adjuvant or administered directly, metformin can arrest cancer progression. Furthermore, its utility extends to age-related concerns, inflammation, and even COVID-19. This review presents the current scenario of repurposing these two drugs, taking into consideration both the long-term benefits and challenges.