Researchers at the University of Houston have made a potential breakthrough in the treatment of Crohn's disease, by shifting the medical focus from simply alleviating symptoms to treating the root cause of the disease.
Crohn's disease is a chronic inflammatory bowel disease that occurs when the immune system attacks the intestinal lining, disrupting the "intestinal barrier." When this lining is damaged and fails to repair itself, bacteria and toxins leak into the body, causing chronic inflammation and disease progression.
Although anti-inflammatory drugs are the standard treatment for flare-ups, only 20% of patients achieve sustained remission with these traditional methods.
In a new study published in the journal Gastro Hep Advances, with the participation of researchers from the University of Houston, Baylor College of Medicine and MD Anderson Cancer Center, a new concept is put forward that the disease originates from intrinsic defects in the epithelial lining itself, and these defects also fuel the abnormal immune response.
The team plans to repurpose two existing cancer drugs, pazopanib and ponatinib, to stop the inflammatory cycle initiated by epithelial cells and allow the intestinal barrier to repair itself naturally.
“This is a paradigm shift in the way we think about disease,” says Dr. Seema Khurana, lead author of the study and professor of biology at the University of Houston. “Current treatments only manage the symptoms because we don’t know the real cause. We believe our research brings us closer to identifying the underlying drivers of disease.”
For three decades, Corana has focused on research into gastrointestinal diseases. Her 2018 research was the first to link the health of the intestinal barrier to the development of Crohn's disease, where she discovered that under chronic stress, the intestines of Crohn's patients begin to kill their epithelial cells instead of regenerating them.
In the new research, the team discovered that the stress signal in the epithelial cells of Crohn's patients never turns off. "In a healthy cell, the stress signal rises and then falls when the stress is removed," says Kurana. "But in Crohn's patients, this signal is always on, which prevents the cell from managing the stress and leads to its death, and this in turn causes more inflammation."
The significance of this discovery lies in the fact that it uses drugs already approved by the US Food and Drug Administration, which reduces the risk of clinical trial failures and bypasses the exorbitant costs (between one and two billion dollars) and long timelines (10-15 years) required by new drugs.
The study relied on patient-derived organoids—miniature organs grown from the tissues of actual patients—which is the modern gold standard for biological research. This ensures that the results are applicable to humans and paves the way for future clinical applications.
Korana concludes: "For a patient suffering from chronic Crohn's disease, they are looking for immediate relief. Our goal was to make our results applicable to real patients as quickly as possible."
