AI identifies life-saving treatment for rare Castleman’s disease

An artificial intelligence (AI) tool has helped identify a life-saving treatment for a patient with idiopathic multicentric Castleman’s disease (iMCD), a rare condition with a poor survival rate and limited treatment options. This condition is a cytokine storm disorder, where the immune system releases excessive inflammatory proteins, causing damage to tissues and organs. Researchers at the Perelman School of Medicine at the University of Pennsylvania used machine learning to analyse 4,000 existing medications and pinpoint adalimumab, a drug already used for conditions like arthritis and Crohn’s disease, as a potential treatment for iMCD. The findings are detailed in a new paper published in the NEJM.

Drug repurposing offers hope for rare conditions

The process of using an existing drug for a new purpose is known as drug repurposing. While diseases may present differently, they can share underlying biological mechanisms, making it possible for the same drug to be effective across multiple conditions. This approach is particularly promising for rare diseases, where research and development of new treatments can be challenging.

The study’s senior author, Dr David Fajgenbaum, an associate professor of Translational Medicine and Human Genetics at the University of Pennsylvania, and the patient’s physician, Dr Luke Chen, a haematologist at Vancouver General Hospital, decided to try adalimumab on a patient with iMCD who was entering hospice care. “The patient in this study was entering hospice care, but now he is almost two years into remission,” said Fajgenbaum. “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.” 

AI platform built on pioneering work

The AI platform used in the study was developed based on research by Chunyu Ma and David Koslicki of Penn State University. It allowed researchers to sift through vast amounts of data to identify potential drug repurposing opportunities.

The study also found that adalimumab targets a protein called tumour necrosis factor (TNF), which plays a key role in iMCD. Patients with severe iMCD had elevated TNF levels, and their immune cells produced more TNF than those of healthy individuals. While Castleman’s disease is relatively rare, with approximately 5,000 diagnoses in the US each year, the study’s findings could have a significant impact. “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 Fajgenbaum. “More research is needed, but I’m hopeful that many of them could benefit from this new treatment.”

The power of combined scientific approaches

The study highlights the value of combining AI, laboratory work, and clinical research. Fajgenbaum and his team are now planning a clinical trial to investigate another repurposed drug, a JAK1/2 inhibitor, for iMCD. Fajgenbaum himself has iMCD and previously discovered his own life-saving repurposed treatment. This experience inspired him to co-found Every Cure, a non-profit dedicated to finding more repurposed treatments for rare diseases using AI.