Discovering and developing new treatments for disease is a challenging, time-consuming, and expensive endeavor. For every drug that eventually makes it to the pharmacy, hundreds of compounds fail to deliver results and millions of dollars are spent without a direct return on investment. However, in these economically challenging times, existing drugs and compounds—whether in development, already on the market, or even ones that have failed clinical trials due to lack of efficacy—are being re-examined by pharmaceutical companies and research institutions. The goal of this approach—called drug repurposing— is to find potential new uses for these drugs.
There are three main benefits to drug repurposing—it’s safer, faster, and cheaper. Since a repurposed drug has already passed a significant number of toxicity and other tests, its risks are better known and the chance of failure is reduced. More than 90 percent of new drugs fail during development, contributing to the high cost of pharmaceutical research and development. A new therapy based on a repurposed drug could benefit patients sooner—ultimately saving and improving more lives.
In the past, drug repurposing efforts were hampered by the lack of a complete drug collection. Fortunately, a comprehensive listing of clinically approved drugs was recently made available by the NIH. Now, in order to make the promise of drug repurposing a reality, Sanford-Burnham researchers are building the world’s most comprehensive library (collection) of repurposed drugs, which can be leveraged against our strengths in stem cell biology, phenotypic cell-based screening, and high-throughput drug screening. Moreover, this library will be made available to other non-profit research institutions to advance translational medicine.
Despite the promise of drug repurposing, serendipitous discovery of new applications for existing drugs happens rarely, and only at the point when people are actually taking them. With the advent of stem cell-based human disease models—called disease in a dish—researchers can now test large numbers of approved drugs for their efficacy against a number of diseases before they reach clinical testing in humans. In this technique, researchers at Sanford-Burnham and elsewhere take skin samples from a patient or healthy volunteer, dial them back developmentally to stem cells, and induce their differentiation into the desired cell type (neurons, for example, if studying Alzheimer’s disease). The advantage to disease-in-a-dish modeling is that it generates large numbers of otherwise hard-to-access cell types, complete with an individual’s genetic and epigenetic make-up—making it a valuable tool for discovering and developing therapies that are more personalized to the individual.
Using cells from a patient with muscular dystrophy and a small library of FDA-approved drugs, Sanford-Burnham scientists have already identified a series of agents that reverse the functional defect causing the disease, providing an initial proof-of-concept for this approach. Spurred on by this exciting data, the team is now developing disease-in-a-dish screens for other genetic diseases.
While we are making substantial progress, one challenge is the incompleteness of the current drug repurposing library available to us. The more complete this library, the greater the chance we will find a drug that can potentially be repurposed to treat a child with a genetic condition like muscular dystrophy or other diseases.
“Regrettably, pharmaceutical companies are not likely to engage in drug repurposing efforts for rare childhood diseases,” Sanford-Burnham’s Layton Smith told Drug Discovery News. “This is in part due to the smaller patient populations and challenges in running clinical trials in these indications. In addition, competition with generic drugs makes this effort commercially unviable, in spite of its great potential to benefit human health. Even if companies were motivated to engage in these efforts, it is very difficult for the pharmaceutical industry to perform the type of screens Sanford-Burnham is doing because of their limited access to patient samples.”
Non-profit research institutes such as Sanford-Burnham, on the other hand, are well positioned to respond to this market and research opportunity.
To learn more about our drug repurposing efforts, please visit Creating the World’s Most Comprehensive Drug Repurposing Library.