Feb. 12 (Bloomberg) -- After screening 4,000 existing drugs, aAItool helped discover a drug that successfully saved the life of a patient with idiopathic multicentric Castleman disease (iMCD). iMCD is a rare form ofillnesses, which has a very low survival rate and limited treatment options.
According to a new paper published in the New England Journal of Medicine (NEJM), a team led by researchers at the Perelman School of Medicine at the University of Pennsylvania utilized an artificial intelligence technique called machine learning toAdalimumab identified as the "best predictor" of new therapies that may be effective in iMCD.. Adalimumab is a self-injectable biotherapeutic drug that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of a variety of diseases, including arthritis and Crohn's disease.
At the same time, the team found that tumor necrosis factor (TNF), a specific protein inhibited by adalimumab, may play a key role in iMCD. They detected elevated levels of TNF signaling in the most severely ill iMCD patients, and further analysis showed that immune cells in iMCD patients produced more TNF upon activation than in healthy individuals.
Based on these findings, the study's senior author, Dr. David Fajgenbaum, Associate Professor of Translational Medicine and Human Genetics at the University of Pennsylvania, and the study's patient's treating physician, Dr. Luke Chen, a hematologist at Vancouver General Hospital in Canada, decided to try this TNF inhibitor for the first time in patients with iMCD. Dr. Luke Chen
"This patient was originally about to go into hospice care in the study, but he has now been relapse-free for close to two years." Dr. Falkinbaum said, "This is not only significant for this patient and for iMCD, but it demonstrates the great potential of machine learning in finding more treatments for disease."
The use of an existing drug for a purpose other than its original use is known as drug repurposing. Many diseases may seem very different in terms of symptoms, prognosis and even cause, but they may share some common underlying links in the body, such as common genetic mutations or molecular triggers, and can therefore be treated with the same drugs.
Dr. Falkinbaum, who himself has iMCD, has been in remission since his research led him to a life-saving repurposed drug more than a decade ago. This experience inspired him to join the University of Pennsylvania and co-found a non-profit organization called Every Cure.Aims to use artificial intelligence to analyze massive amounts of data to find approved drugs as potential treatment options for patients with rare diseases.
The AI platform used in this study was built on the groundbreaking work of Chunyu Ma, a research assistant at Penn State, and David Koslicki, an associate professor of computer science and engineering, biology, and the Hecker Institute for the Life Sciences.
The patient described in this study was originally about to enter hospice care because multiple previous treatments had failed to work.
According to IT House.Idiopathic multicentric Castleman disease is a cytokine storm disease.. Cytokine storm is an excessive and harmful response of the immune system, manifested by the release of too many inflammatory cytokines (proteins involved in intercellular communication in the immune system) that may damage tissues and organs of the body. As a result, patients with iMCD may experience symptoms such as swollen lymph nodes, systemic inflammation, and life-threatening multi-organ failure. Until treatment with adalimumab, they suffered from these problems.
Although Castleman's disease is relatively rare -- about 5,000 people are diagnosed in the U.S. each year -- the study's findings are expected to save the lives of many more patients. "There are probably a few hundred patients in the U.S., and thousands worldwide, who experience this fatal outbreak of the condition every year, as this patient has experienced before." Dr. Falkinbaum said, "While further research is needed, I believe many patients may benefit from this new treatment."
The study emphasizes the importance of combining multiple scientific approaches rather than using artificial intelligence, laboratory work, or clinical research methods alone.
Looking ahead, Dr. Falkinbaum and his team are preparing to initiate a clinical trial this year to evaluate the effectiveness of another repurposed drug, a JAK1/2 inhibitor, on iMCD.
