In a new study, researchers from the UBC Faculty of Medicine and University of Pennsylvania Perelman School of Medicine used a precision medicine approach—combining artificial intelligence, multi-omics and patient-centred strategies—to uncover a lifesaving treatment for a person with idiopathic multicentric Castleman’s disease (iMCD).
This rare inflammatory disease has an especially poor survival rate and few treatment options. The patient could be the first of many to have their life saved by the approach, which could potentially apply to other rare conditions as well.
Detailed in a recent paper published in NEJM, the researchers used machine learning to determine that adalimumab—an FDA-approved monoclonal antibody that treats conditions ranging from arthritis to Crohn’s disease—was the ‘top-predicted’ treatment to work for iMCD. In parallel, the study team found that the specific protein that adalimumab inhibits, called tumor necrosis factor (TNF), was potentially playing a key role in iMCD.
“Often, a simple diagnostic or therapeutic solution is available, but we won’t find it unless we work together.” Dr. Luke Chen
Taking these findings together, the research team decided to try the treatment for the first time in an iMCD patient in Vancouver. The patient, set to enter palliative care at the time before treatment, is now in remission. The study was published on the two-year anniversary of his remission.
“This is a stellar example of the importance of collaboration in rare diseases. No patient or physician should struggle with a rare inflammatory disease in isolation” said Dr. Luke Chen, an affiliate professor of hematology at UBC’s Faculty of Medicine. “Often, a simple diagnostic or therapeutic solution is available, but we won’t find it unless we work together.”
Giving new purpose to existing medicines
The process of using an existing drug for a purpose other than its initial intent is called drug repurposing. Many diseases that appear different in symptoms, prognosis or cause can share underlying links in the body—such as common genetic mutations or molecular triggers—meaning there is the potential to treat with the same drug.
“This is remarkable not just for this patient and iMCD, but for the implications it has for the use of machine learning to find treatments for even more conditions,” said Dr. David Fajgenbaum, an associate professor of translational medicine and human genetics at the University of Pennsylvania Perelman School of Medicine.
Idiopathic multicentric Castleman’s disease is a cytokine storm disorder. In such disorders, an exaggerated immune response releases too many inflammatory cytokine proteins that cause damage to the body’s tissues and organs. Those with iMCD can, as a result, experience swelling of the lymph nodes, inflammation throughout their body and life-threatening multi-organ failure.
While Castleman’s disease is relatively rare – about 5,000 people are diagnosed in the U.S. each year – the findings of this study could save the lives of many more.
“There are probably a few hundred patients in the United States and few thousand patients around the world who, each year, are in the midst of a deadly flare-up like this patient had been experiencing,” said Dr. Fajgenbaum. “More research is needed, but I’m hopeful that many of them could benefit from this new treatment.”
Dr. Fajgenbaum is the co-founder of a non-profit called Every Cure, dedicated to using machine learning for drug repurposing, and Dr. Chen is a member of the scientific advisory board. This study is the latest success story from their collaborative efforts to cure rare inflammatory diseases, and highlights the importance of combining a range of scientific approaches to identify effective treatment strategies, including AI, laboratory work and clinical research methods.
Moving forward, Dr. Chen is developing a program for rare inflammatory diseases that will serve patients and their physicians dealing with rare blood disorders from British Columbia to Atlantic Canada.
“Research in rare diseases is very challenging; we simply can’t match the numbers or funding directed towards common diseases,” said Dr. Chen. “One way to overcome this is to develop networks of expert clinicians and researchers who are ‘thinking outside the box’ to find new solutions.”
Dr. Chen’s work is supported by a philanthropic gift from the Hsu & Taylor Family through the VGH & UBC Hospital Foundation. A version of this story originally appeared on the Perelman School of Medicine website.