"How can you help someone with a disease that’s going to deplete their happiness?”
“You’re a cancer survivor. People talk about that a lot, but they don’t talk about quality of life afterwards. They survived the cancer! But then you flip the coin and on the other side there’s all the health issues that you have to deal with,” says Sarah Knox, PhD, Professor in the Department of Cell and Tissue Biology in the UCSF School of Dentistry. “You don’t think about what’s going to happen if you lose the ability to make saliva.”
The Knox Lab is developing a therapeutic to regenerate damaged salivary glands.Dr. Sarah Knox and her team of researchers study the formation and regeneration of organs. The focus of recent work in their lab is on salivary glands and the cornea.
Radiation therapy is the most common and effective treatment for head and neck cancers. The tumors are carefully targeted with gamma radiation but, despite precautions, the radiation almost always causes permanent damage to salivary glands.
“There is no radioprotective therapy that can block gamma radiation to surrounding tissues. Radiation therapy is the destruction of things that you want to destroy. During administration, it is extremely difficult to avoid damaging nearby structures such as salivary glands,” Dr. Knox said. “There’s some level of success for trying to maintain the tissue, but we’re talking a very small percent. This is why regeneration is such a particular focus for researchers in this field.”
There are other causes of salivary dysfunction, including smoking, diabetes, and certain medications, and autoimmune diseases such as Sjogren’s syndrome. Chronic xerostomia (dry mouth) is a serious health issue that causes oral and digestive problems.
People are often unprepared for the dramatic changes to their lives once they lose the ability to generate saliva. There are numerous dietary restrictions for someone with xerostomia. Eating foods with sharp edges, such as crusty breads, is very painful and causes damage to soft tissue that, in the absence of saliva, is very slow to heal.
In addition to generating moisture, which is essential for tasting food, salivary glands provide the first step of digestion. Food must be moist to move easily through the esophagus to the stomach. Saliva also contains amylase, which breaks starch down to less complex sugars. The absence of saliva transforms eating from something that was enjoyable into an uncomfortable process from beginning to end.
There are additional complications of chronic dry mouth, including increased dental caries and oral candidiasis. Patients with dentures might find wearing them too painful. Activities that require physical exertion are challenging due to a painfully dry mouth that makes even breathing even more difficult. While it’s clear that a sport like running would be too difficult, consider that even talking can be taxing with xerostomia.
Dr. Sarah Knox in her lab on the UCSF Parnassus Heights Campus, July 23, 2024.Dr. Knox said that it’s common for people with salivary dysfunction to carry water or other liquids with them at all times. “I know a man who found that milk coats his mouth better than water, so he brings a bottle of it with him everywhere.”
A primary concern for Knox and her team is finding ways to improve the quality of life for people who have suffered salivary gland damage.
“This niche area can compartmentalize your entire happiness,” Knox said. “Your ability to eat, to talk, the ability to live in a typical way—that you don’t take into consideration at all—is lost. That’s when you say: I didn’t know what I had previously. What am I going to do to get it back?”
The truth is that there is very little that someone can do on their own presently to restore their previous quality of life. The current treatments are palliative with no curative options available.
In 2023, the California Institute for Regenerative Medicine (CIRM) awarded the Knox lab a grant of $2.3M to fund translational research. Knox and her team intend to develop neurogenic hydrogel stimulation of stem cells with a goal of regenerating radiation-damaged salivary glands.
Knox and her team are developing a hydrogel that can be injected into damaged salivary glands in order to stimulate growth of new tissue. The hope is to restore a pre-cancer or pre-disease quality of life. To that end, they have created a company named Hydronovo to further their work in this field. Knox believes that Hydronovo has the vision and composition to be successful.
“Salivary glands are understudied and it takes an all-woman run company to get something going here,” Knox said, laughing. “Obviously my male counterparts also care. But if we can reignite or ignite people’s curiosity about this necessary element required to be happy, then I think that things will move forward very quickly.”
UCSF School of Dentistry is a natural fit for this kind of research, Knox explains.
“We’re doing this in the School of Dentistry because it’s craniofacial. It’s in the head. When most people think of dentists, they think of teeth. But it’s a lot more than that. And if you’ve got a good dentist, they are all about spotting issues in the mouth, such as with mucosa or the tongue.”
Knox was drawn to this area of research initially when she studied the process of organ formation using the salivary gland as the model system. She was amazed by how cells were generated to create the tissue and in the course of her work found a mechanism by which the developing glands did this.
“I thought, could I use this mechanism as an approach to regenerate damaged salivary glands? And through the passion and resilience of my trainees and our interactions with clinicians who work with patients daily, we found it was possible.”
Research is a primary piece of the school’s True North vision, which emphasizes discovery as the thing that will innovate patient care. The education of tomorrow will be informed by the advances made by the researchers presently engaged in pursuit of their ideas.
“Research plays a huge part in taking all these ideas and putting them into the clinic, “Knox said. “Our goal is to translate our basic research strategies that target diseased or damaged tissues, and especially the salivary glands, to the clinic. The ability of the dentist to understand how to help their patient comes down to how the researcher understood what can cure the patient’s condition. Without that understanding the practicing dentist would be stuck in the 1800s.”
