May 2, 2024 – More than 1 million Americans live with Crohn's disease, a chronic and sometimes debilitating inflammatory bowel disease that affects the intestines and causes digestive problems. While some people have mild symptoms or are even symptom-free for periods of time, others suffer from severe abdominal pain, diarrhea, fatigue, weight reduction, anemia, and other life-threatening complications.
There is currently no cure for this disease, and treatment options are sometimes limited. Conventional medications akin to steroids and immunosuppressants can provide relief and slow the progression of the disease, but many patients report that the medications turn into less effective over time or don't work in any respect. Although surgery could also be an option in some cases, each patients and doctors are eagerly looking for recent therapies that may relieve symptoms and in addition result in a greater quality of life.
In recent years, gastrointestinal researchers have focused heavily on solutions for IBD generally and Crohn's disease specifically. Thanks to research funding, gastrointestinal experts across the U.S. have tested recent drugs that fight inflammation and autoimmune responses, and have performed fecal transplants, which might transfer “good” bacteria from a donor's digestive system to enhance gut flora.
In 2024 alone, several developments have been announced that might provide relief in alternative ways. In California, for instance, researchers are developing a kind of stem cell therapy that might help heal the intestinal lining and provoke a positive immune system response. The therapy has shown promising leads to mouse models but has yet to be tested in human clinical trials. But it could represent an option for patients who don't respond well to plain treatments or the most recent drugs.
“Many new therapies and biologics have been developed for IBD over the past decade, but these drugs carry the risk of side effects and, at best, half of patients do not respond. And if they do respond, the longer they take the drugs, the more likely they are to lose that effect,” said Maneesh Dave, MD, associate professor of medication within the areas of gastroenterology and hepatology on the University of California, Davis.
Researching stem cells
Dave, who leads stem cell therapy research at UC Davis, identified other problems with current drugs. Severe unintended effects may cause blood clots in the guts, lungs and legs. These drugs often suppress the immune system, which might result in the next risk of infection and even cancer. So Dave and others are working on solutions to extend response rates, reduce unintended effects and get as near remission as possible by treating inflammation and healing the gut.
In a Study published in January In npj Regenerative MedicineDave and colleagues studied how cells called human bone marrow-derived mesenchymal stem cells (hMSCs) can heal inflammation in mice affected by chronic small intestinal inflammation, which is analogous to Crohn's disease in humans. After administration of the hMSCs, the mice experienced mucosal healing and an immunological response – even weeks after the hMSCs were not present.
“These cells can suppress the immune system and induce regeneration of the intestinal lining, which is quite promising,” Dave said. “There is a precedent for this in Europe, where the cells are already approved to treat certain diseases, but in the US we don't have any proof of this yet, and clinical trials are currently underway.”
While such studies proceed, Dave cautions IBD patients against going to unregulated stem cell clinics that supply therapies which have not yet been proven to work. The FDA has not yet approved any treatments on this area, so stem cell offerings within the U.S. are “still experimental,” he said, and may lead to infections or other serious complications.
Feel the flare-up
When individuals with Crohn's disease have flare-ups, they often report abdominal pain, diarrhea, and sometimes bloody or mucousy stools. This change in symptoms means there may be inflammation within the body – and it must be healed. At Northwestern University, a team of researchers has developed a wireless implantable temperature sensor to detect these flare-ups of inflammation and thus prevent or limit the damage.
“Temperature fluctuations are a hallmark of inflammation, and prolonged inflammation can cause severe damage to the tissue or organ, ultimately leading to disruption of the entire system,” said Dr. Arun Sharma, an associate professor of urology at Northwestern University Feinberg School of Medicine and associate professor of biomedical engineering on the McCormick School of Engineering.
In a Study published in March In Nature Biomedical EngineeringSharma and colleagues tested whether a temperature sensor – a tiny, soft device that rests on the intestines – could provide real-time insights into disease progression and flare-ups in mice with Crohn's disease. The researchers used the sensors to repeatedly track temperature changes for about 4 months and located that the extent of flare-ups may very well be tracked using the warmth signature. This means doctors could potentially act early to assist patients, quite than waiting weeks to check blood, tissue or stool samples.
Now that they've achieved successful leads to mice, Sharma and the research team plan to check the sensor in human tissue that mimics the inflammatory conditions seen in Crohn's disease. These forms of sensors may be useful for patients with ulcerative colitis, one other inflammatory bowel disease, or other conditions with long-lasting inflammatory responses, akin to organ transplants.
“If there was a platform that could monitor the disease outbreak in real time, that would be of great importance so that the treating physician could take appropriate measures in time to improve the situation,” he said. “With the technological advances we have described, this could one day become a reality, so that the quality of life of those affected could be significantly improved.”
Caring for kids
In the United States and Canada, IBD specialists who deal with pediatric patients are working together to search out higher solutions for kids. CAMEO study (Clinical, imaging, and endoscopic outcomes in children with newly diagnosed Crohn's disease) The goal of the research is to grasp why some children receiving standard treatment with anti-tumor necrosis factor (anti-TNF) drugs experience mucosal healing and others don't.
“Few studies have been conducted to treat Crohn's disease in children, and all of the drugs on the market are based on large-scale trials in adults,” said Neal LeLeiko, MD, professor of pediatrics at Columbia University and director of the pediatric IBD program at NewYork-Presbyterian Morgan Stanley Children's Hospital. LeLeiko is the investigator of the CAMEO trial on the NewYork-Presbyterian/Columbia site.
Specifically, researchers hope to search out the most effective anti-TNF dosage for kids, which might vary based on weight. For example, when children receive the drug intravenously and their condition improves, they often gain weight, however the prescribed drug dosage may not change, which could then result in a decline in effectiveness, LeLeiko explained. A critical a part of the study relies on a way often known as “therapeutic drug monitoring,” during which researchers rigorously measure routine blood levels for the anti-TNF drugs and various facets of healing.
“I see too many patients where anti-TNF drugs don't work because their previous doctors didn't know how to use the drugs properly,” he said. “I always say, 'What would I do if it were my child or grandchild?' We need to know the best and safest way to use these drugs in children.”