91视频 Professor Seema Khurana points to a microscopic image showing the expression of a protein of interest in a normal tissue section. Khurana is part of a team focusing on finding treatment for Crohn鈥檚 disease.
Key Takeaways
- In a new study, 91视频 researchers are focusing on a stress signal in cells that prevents the gut lining from healing in Crohn鈥檚 patients.
- By using low doses of existing cancer medications, the team can bypass the decade-long wait for new drug development to bring relief to patients faster.
- The study moves away from traditional anti-inflammatory approaches to a regenerative approach, using patient-derived 鈥渕ini-organs鈥� to prove that the intestinal lining can be taught to repair itself.
91视频 biologists have contributed to a potential breakthrough in treating Crohn鈥檚 disease by shifting the clinical focus from symptom management to addressing a primary underlying cause of the condition.
Crohn鈥檚 disease, a chronic inflammatory bowel disease affecting approximately , involves a cycle where the immune system attacks the epithelial lining, disrupting the 鈥済ut barrier.鈥� When this lining is damaged and fails to repair itself, the barrier is lost and bacteria and toxins leak into the body, fueling chronic inflammation and disease progression.
While anti-inflammatory medications are the standard for treating disease relapses or flares, only about 20% of patients achieve sustained remission through these traditional methods.
In a new study published in , researchers from UH, Baylor College of Medicine and The University of Texas MD Anderson Cancer Center propose a new idea: the disease is driven by inherent defects in the epithelial lining, which also fuels the immune response. By repurposing two existing cancer medications, the team aims to stop the inflammatory cycle initiated by the epithelial cells and allow the gut barrier to repair itself.
鈥淚t鈥檚 a paradigm shift from the way we鈥檝e thought about the disease,鈥� said Seema Khurana, senior author and Moores Professor of biology and biochemistry at UH. 鈥淓xisting therapies primarily manage symptoms because we don鈥檛 know what causes the disease. We believe our research brings us closer to identifying those drivers.鈥�
Targeting the Stress Signal
For nearly three decades, Khurana has been a leading researcher in gastroenterology. Her team鈥檚 2018 research first linked gut barrier health to the progression of Crohn鈥檚 disease, noting that under chronic stress, the intestines of Crohn鈥檚 patients begin killing off their own epithelial cells rather than regenerating.
In the new research, the team found that this dysfunction of epithelial cells furthers disease progression by actively inhibiting epithelial regeneration.
鈥淚n a healthy cell, the stress signal goes up and when the stress is resolved, the signal goes back down. In Crohn鈥檚 patients, this stress signal is always on,鈥� Khurana said. 鈥淲hen the stress signal is always on, the cell cannot manage the stress and undergoes a form of programmed cell death called necroptosis, which further triggers inflammation.鈥�
The team determined that using low concentrations of two cancer medications could be crucial to fixing this. Pazopanib and Ponatinib were found to inhibit the initial cellular stress response signaling and the cell death 鈥� promoting the natural repair and regeneration of the intestinal lining.
Focusing on Pathways to Patient Care
Repurposing existing medications offers a massive advantage in medical development. Using medications already approved by the U.S. Food and Drug Administration reduces the risk of clinical trial failure and significantly bypasses the hefty costs and decade-long timelines associated with new drug discovery.
The study also utilized patient-derived organoids 鈥� 鈥渕ini-organs鈥� grown from actual patient tissue 鈥� which is the modern gold standard for biological research. This approach ensures that the results are highly relevant to human biology, paving the way for future clinical applications.
鈥淚f you had to start from scratch to identify and develop a drug, it takes 10 to 15 years and can cost between $1 billion to $2 billion,鈥� Khurana said. 鈥淔or a patient who is suffering from chronic Crohn鈥檚 disease, they鈥檙e looking for some immediate relief. Our goal was to make our findings much more translatable to real patients.鈥�
