WebMD published a story about a young woman, Maddie, who had spent nine years in wheelchair confinement resulting from a rare metabolic disease related to kidney stones. As her doctor attempted to treat the kidney stones, Maddie’s condition gradually improved, and eventually, she was able to walk unaided. Her doctors kept a close watch on her condition, making requisite changes and adjusting dosage.
Doctors at the Washington, D.C. Institute took notice and wondered: Could this drug be effective for conditions other than kidney stones? Their intrigue led to a larger question: Are there other drugs that can make dramatic changes but are going unnoticed?
Maddie’s story raises a critical issue. Developing a drug for a rare disease is not only expensive and often unprofitable but also time-consuming. Yet there may be viable treatments already sitting on pharmacy shelves. It is estimated that there are about 10,000 rare diseases, with scientists identifying approximately ten to twelve genetic diseases each week.
Dr. Marshall Summar, Director of the Washington, D.C. Rare Disease Institute, explained that rare disease research follows its own rules. There is no cure for most disorders, and despite government incentives such as the Orphan Drug Act, research and development face formidable obstacles: a small population spread worldwide, a ten to fifteen-year wait time, and costs hovering around a minimum of $1 billion.
Dr. David Fajgenbaum, assistant professor of medicine at Pennsylvania University, has found an easier answer. He was diagnosed with idiopathic multicentric Castleman disease, which causes cell overgrowth in lymph nodes and can lead to life-threatening infections or organ failure, with an average life expectancy of about a year. After months of hospital research, his team discovered an overactive pathway in his immune system and decided to test sirolimus, a twenty-five-year-old drug used in kidney transplants that targeted similar pathways. The drug had a profound effect. Nine years later, Dr. Fajgenbaum’s health has been near perfect, and the treatment has helped others with the disease.
However, Dr. Fajgenbaum discovered that sirolimus is not effective on all Castleman patients. He has since become director of the CSTL, an organization devoted to repurposing medications. Over the years, four treatments have been used off-label, with one slated for clinical trial. In each case, researchers used medications already on the market.
Yet Dr. Fajgenbaum acknowledges that thousands of rare diseases have no viable treatments. There is no financial incentive to pursue new uses for old drugs—it is far more profitable to develop new drugs, which remain patent-protected and avoid potential exposure of previous side effects through continued clinical research.
To address this problem, Dr. Fajgenbaum partnered with his friend Dr. Grant Mitchell and experts at North Carolina University to create “Every Cure,” a group leveraging machine learning to sift through approximately 3,000 FDA-approved drugs and 12,000 rare diseases. According to Dr. Fajgenbaum, the drugs near the top of the list appear promising.
Dr. Christine Clovis, Director of Drug Development at NCATS, agrees that the number of rare diseases creates too many obstacles when working with one disease at a time. She hopes to determine how many other drugs have the same capacity as sirolimus to transform patients’ lives.
