Drug repositioning is a strategy for identifying new therapeutic uses for drugs that have already been approved or investigated for other conditions. This approach takes existing medications, whether on the market or previously shelved, and finds new diseases they can treat. The core idea is that a single molecule can often interact with multiple biological pathways. While its primary interaction might treat one illness, its other effects could be beneficial for a different condition.
Investigating these secondary activities forms the basis of drug repositioning, also known as drug repurposing. This method is distinct from traditional drug development, which starts from the very beginning with the discovery of a new chemical compound. This approach applies not only to marketed drugs but also to compounds that failed in late-stage clinical trials. A drug may prove ineffective for its original intended disease but still be safe for human use, making its existing safety data a valuable starting point for exploring other applications.
The Repositioning Process
The journey of repositioning a drug begins with a compound that has a known history. A repositioned candidate has already undergone significant testing, meaning detailed information on its pharmacology, formulation, and potential toxicity is already available. This existing data provides a foundation, allowing the process to bypass the earliest stages of development.
With a potential new use, or “indication,” hypothesized, the drug enters a streamlined development pathway. It begins with preclinical studies, which involve laboratory tests and animal models for the new disease target. The goal is to gather robust evidence that the drug has a genuine effect on the new condition before moving on to human trials.
A primary advantage becomes apparent during clinical trials. Since the initial safety of the drug in humans has often been established, researchers can sometimes skip the initial Phase I safety studies. This allows them to proceed directly to Phase II trials, which focus on assessing the drug’s effectiveness for the new indication. After gathering sufficient data, the drug sponsor submits this new information to regulatory bodies for approval for the new use.
Rationale for Repurposing Drugs
A primary driver for drug repositioning is the established safety profile of existing medications. Any drug approved for human use has already passed extensive preclinical toxicology studies and Phase I clinical trials to assess safety and dosage. This pre-existing safety data lowers the risk of failure during later development, as safety concerns are a common reason new drug candidates are abandoned.
This de-risking contributes to a significantly reduced development timeline. Traditional drug discovery is a lengthy process that can take over a decade, while repositioning can bypass several years of early-stage research. This acceleration means that beneficial treatments can reach patients much more quickly.
The shorter timeline and reduced trials also result in lower development costs. The initial discovery, synthesis, and extensive safety testing phases of traditional development account for a substantial portion of the overall expense. Avoiding these steps makes repositioning a more financially viable strategy, which is impactful for developing treatments for rare and neglected diseases.
Methods for Identifying New Uses
Scientists employ several strategies to uncover new therapeutic roles for existing drugs. One method is the use of computational approaches, often called in silico analysis. This involves using computers and artificial intelligence to mine massive databases containing information on drug structures, gene sequences, and disease pathways. By identifying unexpected connections, these algorithms can predict promising new drug-disease pairings.
Another method is experimental screening, which takes a more direct approach. In this strategy, libraries of existing drugs are systematically tested against various disease models in the laboratory. This can involve applying the drugs to cell cultures or using other biological assays to see if a compound produces a desirable effect. High-throughput screening technologies enable researchers to perform these tests on a massive scale.
A third source of discovery comes from clinical observation, sometimes referred to as serendipity. In these instances, a new use is discovered by chance when patients taking a drug for its approved purpose report unexpected but beneficial side effects. Alert clinicians who notice these patterns can initiate further investigation into whether the drug could be formally developed for this observed positive effect.
Notable Repurposed Drugs
One of the most well-known examples of drug repositioning is sildenafil. Originally developed to treat hypertension and angina, a type of chest pain, the drug was designed to act as a vasodilator, relaxing blood vessels. During early clinical trials, it showed little effect on angina, but male volunteers reported the unexpected side effect of marked penile erections. This observation led the company to pivot its development strategy, and sildenafil was eventually approved and marketed as Viagra for erectile dysfunction.
Minoxidil provides another example of repurposing driven by clinical observation. It was first introduced as an oral medication to treat very high blood pressure. Doctors and patients soon noticed a side effect: excessive hair growth. Researchers realized this effect could be harnessed for a different purpose. This led to the development of a topical formulation of minoxidil, now widely known as Rogaine, to treat pattern hair loss.
The story of thalidomide is more complex. First marketed in the late 1950s as a sedative and an effective treatment for morning sickness, it was soon discovered to cause severe birth defects. The drug was withdrawn from the market, but subsequent research revealed it had potent immunomodulatory and anti-angiogenic properties, meaning it could interfere with the growth of new blood vessels. These discoveries led to its successful and carefully managed repurposing as a treatment for a complication of leprosy and for the blood cancer multiple myeloma.