Regenerative medicine provides hope for IBD patients with perianal disease

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 final blog post recapping the presentations from the 2020 IBD Innovate.

Crohn's disease that affects the perianal area is challenging to treat. This complication of Crohn's disease affects 25% of patients. Perianal Crohn's disease can lead to the formation of fistulas, which are abnormal connections between an organ and the skin, or between two organs. In some cases, the Crohn's disease can also affect the anal canal (the last part of the large intestine). For patients, this can be quite painful and lead to a severe decrease in quality of life. When the disease has advanced and includes the anal sphincter (which controls the release of stool from the body), it can even result in fecal incontinence. 

Currently there are limited options to treat perianal Crohn's disease. Biologics might be used in some cases and may work well to tame inflammation. However, the open tracts of fistulas might not improve with medication. That's why as many as 90% of patients will need surgery to treat perianal Crohn's disease. The problem is, while there are many different surgical options, as Dr. Amy Lightner pointed out during IBD Innovate, that's actually an indication that "no one particular option works very well."

Dr. Lightner, Associate Professor of Surgery in the Department of Colon and Rectal Surgery at Cleveland Clinic, gave a presentation exploring new options in the management of complicated perianal IBD and even mild-to-moderate IBD. During her presentation, she described the quality of life for her patients with multiple fistulas as very poor and pointed out that surgery doesn’t create remission. In about 20% of cases, creating a temporary ostomy is needed to manage fistulas. In another 20%, a permanent ostomy with removal of the rectum is ultimately needed.

Using stem cells to heal fistulizing disease

In 2003, the first case report was published in treating an IBD patient with a rectovaginal fistula with mesenchymal stem cells (MSCs). After three months, the patient’s fistula was healed. After that, multiple trials were done all over the world with different types of cells to heal fistulas. What's been learned through all this research is that MSCs to treat perianal Crohn's disease are safe, are associated with few adverse effects, and are effective. 

Dr. Lightner reported on several small studies using MSCs to treat fistulas:

• In a Phase 1 trial at the Mayo Clinic, which used MSCs to treat 12 patients with fistulae, 83% were healed by six months.
• In another small study, patients received one injection of MSCs. After one year (52 weeks), most patients stayed in remission and did not have another fistula form.

The procedure to receive MSCs is minimally invasive, especially when compared to surgeries normally done to treat perianal Crohn's disease. It is an outpatient surgical procedure: the fistula tract is cleaned out and closed with a single suture and the cells are injected. Importantly, as Dr. Lightner pointed out, there is no risk of incontinence with these procedures.

With the success of these trials, researchers are looking to use MSCs in treating other types of IBD. Another application of MSCs that Dr. Lightner's team is working on is in recto-vaginal fistulas and fistulas in pelvic pouches (j-pouches). The procedure is similar in these patients: the fistulas are cleaned out, the internal opening is closed up, and MSCs are injected into the area.

The next opportunity that Dr. Lightner identified is in the use of MSCs in ulcerative colitis and Crohn's colitis. There are two trials that are beginning now in patients with mild-to-moderate forms of IBD. In these trials, the cells are injected into the submucosal layer of the intestine during a colonoscopy. This technique is also planned for use in patients who are experiencing pouchitis in a pelvic pouch. "Basically," Dr. Lightner summarized, "the concept is local delivery of cells right to the area of either fistula inflammation or intestinal inflammation."

Limitations of stem cell therapy

However, even though the results are promising, Dr. Lightner advised some caution, because there are limitations to this therapy. Not all hospitals are equipped to harvest MSCs and shipping to treatment sites isn't a simple solution because cells must be used within hours. For the therapy to be available to more patients, researchers will need to derive a procedure to freeze and thaw the cells. 

Another problem is the cost of treatment with MSCs. The therapy is expensive and is not currently covered by insurance. If these therapies are approved for use, the question of insurance coverage is still an open one.

The last issue is one of efficacy. The range of effectiveness for the various trials range between approximately 50% and 80%. Dr. Lightner pointed out that there is variability between cell donors as well as differences between disease states (including Crohn's disease and ulcerative colitis). Identifying ideal donors and matching the right donor cells to the right patient is an important next step. "To really push the efficacy of clinical trials to that 90%, we need to be thinking about this variability, and identifying the ideal donors, and identifying ideal ways to deliver our cells," Dr. Lightner said.

Even so, for patients who have severe disease that's limiting their quality of life, stem cell therapy is offering some hope. For those that can enroll in the trials, it's an option that's open to them when other therapies have failed. Dr. Lightner concluded, "When patients come for our trials, they're very excited that there's something else that could be out there that may offer them a chance for healing. So, it's been really a pleasure treating these patients and getting some of these trials off the ground."

Read the first and second posts in this series from IBD Innovate here:

Providing a brighter future in pediatric Crohn’s disease

Throwing light on a potential new treatment for ulcerative proctitis

Amber Tresca is a writer for the Crohn's & Colitis Foundation. She is the IBD expert for VeryWell and hosts the About IBD podcast.