Drug Repurposing: The New R&D
It is widely accepted that innovation is the cornerstone of modern medical development.1 As human diseases have evolved over the past decades and centuries, it has been innovation – this willingness of researchers and clinicians to convert new ideas into practical applications – that has led to the development of novel medicines and treatments.2 In 1922, for instance, Banting and Best developed insulin as an innovative cure for diabetes after conducting thousands of experiments at the University of Toronto. The development of the smallpox vaccine by Jenner in 1796 was also a groundbreaking innovation, ultimately leading to the eradication of a disease that has plagued humanity since before the dawn of civilization.3 While Banting and Best arrived at their solution through repeated experimentation, Jenner did so through his astute observation of milk maids in his area. Although the methods by which these scientists arrived at their innovations were vastly different, the gravity of their contributions continues to be felt in this modern age. In fact, it is the idea of these differential pathways that is key to medical innovation today.
““R&D is arguably not the form of innovation currently most needed in today’s cash-strapped healthcare systems.””
The current means of innovation in modern medicine is what is known as research and development (R&D), the serendipitous process of drug testing and experimentation that has led to the vast majority of pharmaceutical therapies on the market today. Unfortunately, R&D is arguably not the form of innovation currently most needed in today’s cash-strapped healthcare systems.4 The process of R&D costs pharmaceutical companies billions of dollars per year, with a success rate of only 4.1%. To accommodate for this costly development process, the few drugs that do make it to market are given inexorably high prices, making them unattainable for many who need it.
““Cost-effective and efficient, drug repurposing represents a promising means of finding treatments for the thousands of untreatable rare diseases that persist in the modern healthcare system today.””
To counter this problem, it is important to remember that, as Banting and Jenner demonstrated, there are many paths to innovation. Innovation is not only about the advent of new therapies, but also the repurposing of existing solutions in original contexts. Embodying this holistic idea of innovation, drug repurposing is a scientific approach to drug development that hinders upon the identification of novel applications for existing treatments.4 The repurposing of the natalizumab monoclonal antibody cancer drug, for example, has led to one of the most efficacious treatments for multiple sclerosis today.5 Cost-effective and efficient, drug repurposing represents a promising means of finding treatments for the thousands of untreatable rare diseases that persist in the modern healthcare system today.
““Of the 7,000 different rare diseases in existence worldwide, only 400 currently have licensed treatments.””
The Challenge of Rare Diseases
Rare genetic conditions are a target of great potential for drug repurposing. Of the 7,000 different rare diseases in existence worldwide, only 400 currently have licensed treatments.6 This means that there is a large treatment gap for millions of people with little hope for disease-altering clinical support. With the development of genomic sequencing, however, the repurposing of drugs has become a promising area of exploration.6 Genomic sequencing has enabled scientists to quickly match existing drugs to the impaired biochemical pathways associated with various diseases.7 In doing so, researchers can save millions of dollars on the R&D that would go into the development of a novel therapeutic.
““...researchers can save millions of dollars on the R&D that would go into the development of a novel therapeutic.””
How Drug Repurposing Works
Drug repurposing works in two distinct phases: candidate drug identification and drug effect testing.4 Candidate drug identification is the identification of potential drugs for repurposing, achieved through simple trial and error, advanced text mining approaches, or the analysis of gene expression patterns. Historically, trial and error have been the main driving force behind drug repurposing. In 1964, for example, Israeli physician Dr. Jacob Sheskin discovered a novel treatment for leprosy when he prescribed to a patient a drug typically regarded as a sedative.8 Instead of simply putting the patient to sleep, the drug actually mitigated many of the leprosy symptoms experienced by the individual.8 This serendipitous case is the most primitive example of drug repurposing but demonstrates the potential it holds as a therapeutic strategy.
““Today, researchers focus on more targeted ways to look for drug candidates to repurpose based on knowledge of disease pathology and drug mechanisms.””
Today, researchers focus on more targeted ways to look for drug candidates to repurpose based on knowledge of disease pathology and drug mechanisms.4 Modern screening technology, in conjunction with the wealth of data available with the rise of Big Data, has paved the way for the development of a systematic way to repurposing drugs.9 Text mining, for example, has allowed bioinformaticians to search published scientific literature for similarities and links between diseases and drugs.9 Computer algorithms that go beyond simple connections in sentence structure have also been developed to infer connections between entities that are not explicitly mentioned in text. While such technologies still require a great deal of further development, they have nevertheless provided a gateway to many repurposing opportunities that were previously unavailable.
Transcriptomics
Transcriptomics represents an area of study that provides a backbone for the research surrounding drug repurposing.10 Transcriptomics is the study of all of the genes active in the body’s cells, also known as an individual’s genetic makeup. The activation of genes in a cell determines how it functions. Cells, in turn, underlie the formation of tissues, organs, and organ systems in the body, which underscores the importance of such studies. Many genetic diseases arise when the expression of certain genes in an individual is different from those of unaffected individuals.11 This produces a “transcriptomic signal” in certain genes in the body that are differentially expressed.10 A new approach to drug repurposing relies upon the identification of transcriptomic signals of specific drugs that would act to oppose the signals of the disease.10 Theoretically, this would allow the drug to reverse the disease signal and normalize the gene expression in affected cells, thereby eliminating disease symptoms.4
““While drug repurposing projects are estimated to be delivered successfully in approximately 30% of cases, the same statistic in classical drug development lies in the single digits.””
Success rate of drug repurposing
One of the greatest advantages of drug repurposing is its ability to bypass many of the costly and time-consuming steps of the drug development process, including research and design, preclinical trials, and clinical trials.5 Removing such steps in the drug development pathway helps reduce the time drugs take to reach the clinic, as well as their cost of doing so. The success rate of identifying promising drugs from drug repurposing studies is also much higher compared to novel therapeutics.5 As a result of the greater depth of knowledge regarding the candidate drug’s behaviour in humans from the initial stages of the project, repurposed drug candidates are much more likely to be accurately screened for its potential as a successful therapy.5 While drug repurposing projects are estimated to be delivered successfully in approximately 30% of cases, the same statistic in classical drug development lies in the single digits.5
Conclusion
As a result of its relatively small financial burden, high success rate, and recent developments in its associated technologies, drug repurposing is a field of drug development that is rapidly expanding. Beyond pharmaceutical companies, biotechnicians, academics, and clinicians are all able to play a significant role in pushing this innovation. Recently, patient groups and healthcare startups have also begun to take note of this field and are actively raising funds to drive this promising area of research. Although in its beginning stages, the potential for this burgeoning field is very great indeed.
Works Cited:
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6. Hughes-Wilson W, Palma A, Schuurman A, Simoens S. Paying for the Orphan Drug System: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments?. Orphanet Journal of Rare Diseases. 2012;7(1):74.
7. Genomic medicine: Sequencing diagnoses disease. Nature. 2012;482(7383):9-9.
8. Sheskin J. The Case for Invisible Leprosy. International Journal of Dermatology. 1975;14(5):345-346.
9. Colvis C, Austin C. The NIH-Industry New Therapeutic Uses Pilot Program: Demonstrating the Power of Crowdsourcing. Drug Repurposing, Rescue, and Repositioning. 2015;1(1):15-16.
10. MYC Transcriptomics. Transcriptomics: Open Access. 2013;02(01).
11. Mackay-Sim A, Silburn P. Stem cells and genetic disease. Cell Proliferation. 2007;41:85-93.
Cite This Article:
Lin S., Chan G., Palczewski K., Lewis K., Ho J. Drug Repurposing: The New R&D. Illustrated by P. Taarea. Rare Disease Review. November 2017. DOI:10.13140/RG.2.2.30702.51521.
