children and teens ulcerative colitis Thanks to the invention of several new drugs for this type of inflammatory bowel disease, there are far more treatment options than there were 10 years ago. However, not all drugs are effective for all patients, and it may take weeks or months of trial and error to control symptoms.
Pediatric gastroenterologist Dr. Michael Rosendirector of Pediatric Inflammatory Bowel Disease and Celiac Disease Center in Stanford Medicine Children’s Healthwork with your team to care for young patients who: crohn’s disease, ulcerative colitis and celiac disease, all of which can cause inflammation in the intestines. We also conduct research to understand the biology of these conditions, devise better treatments, and advance precision medicine for these diseases.
People with ulcerative colitis experience unpleasant symptoms such as intestinal pain, frequent bloody diarrhea, weight loss, anemia, and fatigue. Multiple parts of the intestine, including the epithelial barrier (cells lining the intestine), are compromised, resulting in an overactive immune response, likely responding more to changes in the bacteria living in the colon than to the patient’s own cells. Masu. The intestinal lining becomes inflamed and ulcerated, leading to blood loss.
Rosen said we know that all of this is caused by environmental factors, which are not fully understood, in people who have a genetic risk for the disease. “This is a complex interaction of genes and environment that causes dysfunction of the lining of the colon barrier, an unhealthy microbiome, and an exaggerated immune response.”
Recently, Rosen and his colleagues have devised methods to predict how individual patients will fare in the long term at the time of diagnosis. His latest research showed that the activity of two specific genes in the rectal tissue of newly diagnosed patients predicted the outcome of the patient’s disease one year later. They hope to use these discoveries to identify patients who need more advanced treatments and apply the right treatments more quickly.
In a recent Q&A, Rosen discussed the latest research, how he works with families to treat ulcerative colitis in children, and how this research may impact future treatment strategies. Let’s talk about something.
Why is ulcerative colitis not easy to treat?
We usually start treatment with a drug that has been around for a long time, a 5-aminosalicylate drug, which is usually taken orally and is overall very safe. Depending on the severity of the initial disease, corticosteroids may be added. These are not good long-term options due to their side effects, but they can put out the flames of inflammation. We are slowly weaning the patient off steroids in hopes that the 5-ASA drug will prevent flare-ups of inflammation.
If that doesn’t work, the next step is to try IV biologics, such as antibodies that counteract the effects of inflammatory substances called . tumor necrosis factor.
Why was your new study important?
We investigated patterns of gene activity at the time of diagnosis in tissues of patients with ulcerative colitis. We focused on genes involved in the immune response in the colon lining and tried to use that information to predict who would respond to her 5-aminosalicylate drug. By combining patient gene expression information with clinical measurements such as hemoglobin levels, which measure anemia, and symptom severity at diagnosis, we can better predict who will require stepped treatment. I found out that it can be done. This improves current methods for identifying patients who require more intensive treatment. This method requires waiting four weeks after diagnosis to confirm the patient’s status.
How do children and families benefit from such predictions?
Families may be discouraged by the idea of trying a drug that has only a 30 to 40 percent chance of being effective. If you can say, “She has a 60% chance of this working for your child,” that’s a huge deal. Or if we know that a patient only has a 10% chance of success with a particular drug, we will probably try a different drug. We need to further validate the study results, but once validated, patients can be freed from long-term or repeated doses of corticosteroids, and the longer a corticosteroid is used, the more toxic it becomes and the normal We hope that you will be able to return to your daily life quickly.
Ultimately, we need better tools to choose from a growing list of effective treatments. To do this, you will be able to understand what works for the patient in front of you, not what works for her 50% of patients. This brings us closer to precision medicine.
You have measured the activity level of a particular gene that is associated with a patient’s disease outcome. What insights have you gained into the biology of ulcerative colitis?
We are excited about new discoveries related to another gene, RORC. This gene was predicted to have higher activity in ulcerative colitis due to its role in the immune response in ulcerative colitis. Surprisingly, we found that levels were lower in patients with poor outcomes, including the worst outcomes when the colon was surgically removed. This was really puzzling.
Using techniques that allow us to look at specific tissues and individual cells, we can see that this low RORC signal is typically coming from the epithelial cells lining the intestine, rather than from the immune cells where the gene is thought to be functioning. got it. This is very surprising to us and opens the door for future investigations.
All of our treatments for ulcerative colitis target the immune response. There are no existing treatments aimed at improving the health of the cells lining the colon. But for a colon affected by ulcerative colitis to heal, those cells need to grow back. Our next goal is to understand how to maintain healing in the intestinal lining and develop treatments to support that process.
For more information about the Pediatric IBD and Celiac Disease Center, please visit: ibdceliac.stanfordchildrens.org.