Drug Resistance Signature Discovered in Crohn’s Disease
By mapping out more than 100,000 immune cells in patients with Crohn’s disease, Mount Sinai researchers have discovered a signature of cells that are involved in a type of the disease that does not respond to treatment
The study analyzed biopsy samples of inflamed and uninflamed Crohn’s disease lesions on small intestine tissue as soon as it was removed from patients. Researchers used single-cell RNA sequencing and CyTOF technology to look into the intestinal lesions in real time on a single- cellular level, identifying the immune cells and circulating blood cells and their interaction in and around the lesion, and mapping a landscape of thousands of cells in the lesion.
The analysis found a signature of precise cell types, never previously identified, that correlates with a patient’s resistance to the standard therapy for Crohn’s disease, an anti-inflammatory drug called a TNF inhibitor. A TNF inhibitor is the major agent given to patients with moderate to severe Crohn’s disease, but about 40 percent of patients who take the inhibitor end up either not responding to it or having their Crohn’s worsen.
“Single-cell profiling could transform drug discovery,” said co-corresponding author Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, Mount Sinai Professor in Cancer Immunology, Co-Director of the Cancer Immunology program at The Tisch Cancer Institute and Director of the Mount Sinai Human Immune Monitoring Center. “It’s really going to give us much more clarity into inflammatory bowel disease and why patients are resisting and what else we could be targeting.”
Having a signature to identify patients who will fail on the inhibitor is helpful to avoid surgery and complications. Based on this study’s results, researchers have already developed a clinical trial that will test whether it’s possible to find the signature in a blood test when a patient is diagnosed with inflammatory bowel disease. If so, doctors could avoid using a TNF inhibitor and instead use other biologics that will work for that patient.
Read full article at https://www.mountsinai.org/about/newsroom/2019/drug-resistance-signature-discovered-in-crohns-disease