Throwing light on a potential new treatment for ulcerative proctitis
Published: December 22, 2020
On November 17-18, 2020, the Crohn’s & Colitis Foundation hosted its third annual IBD Innovate: Product Development for Crohn’s & Colitis™ conference. This meeting brings together researchers, start-up companies, industry companies, accelerator organizations and more who are committed to accelerating the discovery and development of novel products with the potential to address the unmet needs of patients with IBD. This is the second of three blog posts recapping the presentations from the 2020 IBD Innovate.
It is estimated that over a million people in the United States are affected by ulcerative colitis. When we look at the global picture of IBD, however, it’s three times more common than Crohn’s disease. Within those diagnosed with UC, there is a large group of patients who are often underserved because their disease is not severe. When disease is located in the last 15 centimeters of the colon, it's officially termed ulcerative proctitis. Between 25% and 55% of patients with ulcerative colitis are diagnosed with ulcerative proctitis at diagnosis. Patients with ulcerative colitis that is not advanced or serious enough to need treatment with biologic medications are often not included in clinical trials for these drugs.
There has been intense interest in how the microbiome of the gut may interact with IBD. The microbiome is all the bacteria, fungi, viruses, and other microbes that live in our bodies naturally. Researchers are seeking to understand how changing the makeup of the bacteria in the gut can affect the development and the course of IBD. So far there is not much evidence that can be used to help patients and providers make decisions. It is not yet known how to shift the microbiome to help treat IBD.
What is known, is that in some cases, antibiotics can be helpful, in some cases, for managing inflammation or treating complications. However, there are significant limitations with this treatment approach. It is a short-term measure at best because tolerance to antibiotics is low and associated with the potential for adverse effects. Additionally, there is still a lack of understanding as to why some antibiotics may help for some patients at certain points in their disease journey but not others. Antibiotics are used to treat infections and kill off bad bacteria, but they also have the effect of altering the gut microbiome. Both "good" and "bad" bacteria are killed. The effects on individual patients can vary from being beneficial to leading to worsened symptoms.
During IBD Innovate, Dr. Gil Melmed, Co-Director of the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center, explored the potential for a device to fill a treatment need for people who live with a less severe form of IBD.
Dr. Melmed pointed out that the results seen in IBD with certain antibiotics has put some weight behind the idea of shifting the microbiome. Some of the ideas that are active areas of research include probiotic supplements and fecal microbiota transplants. However, we do not yet know how to effectively use these approaches to treat ulcerative colitis. Let alone how changing the microbiome could be fine-tuned to help groups of patients or even individual patients.
UV light therapy in the treatment of ulcerative colitis
There has been an absence of innovations in treatment for mild ulcerative colitis in recent years. Current therapies have drawbacks that include daily dosing, side effects, and lack of efficacy for some patients. This presents an opportunity in the development of new approaches for treating mild ulcerative colitis.
One of these opportunities, and the subject of research by Dr. Melmed and others, is the use of ultraviolet (UV) light. "If you see a mucosal disease, and it is within reach of UV waves that might be brought directly to the colon, characterized by inflammatory pathways…it may be modulated by light," Dr. Melmed said.
UV light is outside of the spectrum of light that can be seen with the naked eye. It is already known that UV light is broadly anti-microbial. Photo therapy, which utilizes UV light, is used widely to treat inflammatory skin conditions, including psoriasis, eczema, atopic dermatitis, and vitiligo. In fact, it is a first- or second-line therapy for several skin conditions and has been shown to be safe during pregnancy. It is also known that some inflammatory skin conditions, like psoriasis, may have overlapping inflammatory pathways with IBD.
This led to a question: why only use this light on the surface of the skin? If the inflammatory pathways are similar between IBD and skin conditions, doesn't it stand to reason that UV light would also work internally?
The reason may lie in the development of the right type of technology along with an understanding of the exact wavelength of light to use. UV light can penetrate the mucosa, the innermost layer of the digestive tract. However, the creation of light emitting diodes (LEDs) that can both emit UV light and be small enough to be inserted into the body (namely into the rectum) has only come about in the last few years.
UV light comes in various wavelengths, with the shorter wavelengths being able to penetrate deeper into the mucosa of the colon. However, the shorter the wavelength, the greater the risk of the light damaging the DNA of human cells. That led Dr. Melmed and his team to look for the "sweet spot" of a wavelength of light that would be effectively antimicrobial but also not damage cells. Upon finding that, the next steps are in creating a device to use in the rectum and to begin testing.
Dr. Melmed's team has started work on testing the safety of applying UV light to the colon in mice. Their initial results show that after applying the light to the mice, no evidence of damage or injury to the mucosa was found. As far as creating a device, two have been developed: one that can be used in the respiratory tract and one that can be used in the rectum. The rectal device, which will deliver light to the end of the colon, is in the prototype stage and is ready for clinical trials. A study to understand the dose needed is planned.
Dr. Melmed summarized his work by saying, "We also recognize that there may be local antimicrobial effects that is a part of the pathogenesis of ulcerative colitis. And I propose to you that this may be an opportunity to address this unmet need of requirement that we have more safe, effective, and low-cost therapies."
As a patient who was first diagnosed with ulcerative proctitis, which eventually spread to become pancolitis, I couldn’t help but wonder if this technology would have helped me in the early days of my disease. Even though in the beginning, my disease was in my rectum, my quality of life was affected significantly and the only treatments available to me were oral medications that had side effects. Patients always prefer to have more treatment options, and this technology offers a novel therapy with some significant advantages for patients with mild disease.
You can read the first and third posts in this series from IBD Innovate here:
Amber Tresca is a writer for the Crohn's & Colitis Foundation. She is the IBD expert for VeryWell and hosts the About IBD podcast.