Stem cells could be ‘revolutionary treatment’ for swallowing problems after cancer therapy
Researchers at UC Davis Health have initiated a clinical trial using stem cells to address swallowing problems associated with tongue injury from cancer treatment.
The REVIVE trial will evaluate a new technique where researchers inject stem cells from a biopsy of patient’s thigh muscle into the patient’s tongue. The researchers hypothesize that the stem cells will fuse with existing muscle fibers to strengthen tongue muscles and improve ability to swallow.
The trial follows positive data from a phase 1 study of this approach, according to Johnathon David Anderson, PhD, assistant professor at UC Davis Institute for Regenerative Cures.
“The phase 1 data looked very promising, and if that trend in the data holds true for the phase 2 and phase 3 trials, we would be looking at a revolutionary treatment for patients with dysphagia that would be unparalleled,” Anderson told Healio. “That’s the big hope — that’s the promise of stem cell therapies.”
Anderson spoke with Healio about the positive phase 1 results, the current challenges to enrollment in the phase 2 study, and the potential of this approach to mitigate this unpleasant adverse effect of cancer treatment.
Healio: What inspired you to study this?
Anderson: Patients with dysphagia have a horrible quality of life — the patients we treat get head and neck cancer, and they fear for their lives. Then they receive cancer treatments such as chemotherapy, radiation or surgery. Many patients survive and initially everything looks good in terms of their health. However, slowly and increasingly over time they can have issues with the tissues that surrounded the tumor because the radiation causes progressive collateral damage.
What is perhaps not intuitive about this process is the cancer treatments result in successive waves of tissue damage and remodeling that take place over the span of years and even decades. As a result of this cancer treatment toxicity, muscles around the base of the tongue and throat atrophy and eventually start to develop increasing amounts of scar tissue. Eventually, it can become very challenging for patients to swallow their own saliva, much less food. They can have trouble talking and socializing, and sometimes this can result in depression. Further, some of these patients experience additional sequalae such as aspiration pneumonia, and sometimes become dependent on feeding tubes to maintain adequate nutritional intake.
One of the current standard-of-care treatments for these patients is tongue exercises at home. It’s helpful, but it doesn’t stop the disease from progressing. It just lessens the speed of the progression.
This new stem cell therapy approach got its start a number of years ago, when UC Davis recruited Jan A. Nolta, PhD, to run a stem cell therapeutics program. Many researchers in the field of regenerative medicine have high hopes that stem cell therapies may represent a new paradigm shift in how we treat patients.
The person running our clinical trial, Peter C. Belafsky, MD, MPH, PhD, is considered one of the key innovative leaders in the field of dysphagia and swallowing disorders. Belafsky and Nolta developed an intriguing idea: what if we could use the patient’s own stem cells to help them regenerate their lost muscle tissue — the idea being that these muscle stem cells would infuse and engraft into the patient’s muscles in the base of their tongue, thereby adding size and contractile strength to one of the critical muscles involved in an effective swallow.
Another interesting aspect of this story is that some of Belafsky’s patients with dysphagia provided the initial funding to get this project off the ground. With these patients’ generous support, none of this would have been possible. We then joined forces with Cook MyoSite to take this idea through the clinical trial process. Recently, we’ve added another partner, the California Institute for Regenerative Medicine, which awarded us an $11 million grant to test these muscle stem cell therapies in a phase 2 clinical trial. We’ve been blessed to have such great partners throughout this whole process.
Healio: How is this being evaluated in a human population?
Anderson: Once patients are screened and found to be eligible to participate in the trial here at UC Davis, we acquire a small piece of their muscle tissue via a biopsy of their thigh. We send the biopsy to MyoSite, which isolates and expand the muscle stem cells from the muscle tissue. Eventually, they end up with hundreds of millions of these muscle stem cells, which are frozen and shipped back to Belafsky, who injects them in several locations of the patient’s tongue. Belafsky repeats this injection procedure one more time after about 4 to 6 weeks after the initial administration. After that, patients are followed for 2 years so we can closely assess the safety and effectiveness of this therapy. I should also mention that we have a partner site at University of California, San Francisco, which is headed up by an outstanding dysphagia physician, Clark Rosen, MD.
Healio: Who would be eligible to participate in the trial?
Anderson: Patients need to have a history of successful treatment for oropharyngeal cancer and be 24 months out from their treatment. Additionally, patients must be experiencing mild to moderate swallowing issues. So, for example, patients must be able to consume over 50% of their food via mouth, as opposed to a feeding tube, in order to be eligible for this study.
Healio: How did this treatment perform in the phase 1 trial?
Anderson: What we saw was quite remarkable. This disorder is generally progressive, so patients experience a decrease in swallow function over time. If we had a therapy that just kept them in a steady state, with no worsening over time, that would be a huge win for these patients. Interestingly, in the phase 1 study we saw an improvement in the tongue strength of these patients at 1 year out from injection with the therapy. This is an outstanding finding that, if it holds true for this phase 2 trial and beyond, would be a game changer for these patients. Having said that, phase 1 studies are generally smaller and mainly powered to assess the safety of such therapies. It’s really not until the phase 3 trials that we get a robust sense of the therapy’s true efficacy.
Healio: Is there anything else you would like to mention?
Anderson: We’re still enrolling patients, and anyone interested can reach out to us at HS-ENTStemCell@ucdavis.edu. Even though this is a placebo-controlled trial, we will offer the stem cell therapy to patients in the placebo group for free at the end of their participation. In addition, we have some funds available to offset some of the costs for patients traveling from outside the area.
For more information:
Johnathon David Anderson, PhD, can be reached at UC Davis Institute for Regenerative Cures, 2921 Stockton Blvd., Sacramento, CA 95817; email: HS-ENTStemCell@ucdavis.edu.
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Clinical trial for patients with swallowing difficulties after cancer treatment (press release). Available at: https://health.ucdavis.edu/news/headlines/clinical-trial-for-patients-with-swallowing-difficulties-after-cancer-treatment/2023/02. Published Feb. 28, 2023. Accessed March 30, 2023.
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