Three Promising Developments For Treating Radiation-Induced Xerostomia

Xerostomia, also known as dry mouth, is a common side effect of radiation therapy, a treatment method for cancer in the head and neck regions. Radiation therapy can cause irreversible damage to the salivary glands, which impacts their ability to produce sufficient and/or high-quality saliva. 

 

Without sufficient saliva, both oral health and general health can quickly deteriorate, resulting in increased dental caries and infections, difficulty chewing, swallowing, and talking, halitosis, change in taste, sore throat, and more. The combination of these dry mouth symptoms can significantly diminish patients’ quality of life. 

 

Why Research For Radiation-Induced Xerostomia Treatment is Important

Traditional, 3D conformal radiation therapy results in long-term xerostomia in up to 80% of patients, while more modern radiation techniques result in long-term xerostomia in over 40% of patients.

 

After radiation, doctors and dentists work with their patients to minimize the discomfort caused by xerostomia. There are two main methods for doing this: 

 

• Stimulating the salivary glands to produce more saliva 
• Using saliva substitutes

 

The first option is not always suitable for patients who have undergone radiation therapy, as their salivary glands may be too damaged for stimulation. Saliva substitutes, on the other hand, provide temporary relief from dry mouth symptoms, but don’t treat the underlying cause of malfunctioning salivary glands. 

 

Similarly, lifestyle changes such as drinking more water, using a humidifier at night, and reducing alcohol, nicotine, and caffeine intake are minimally effective and don’t offer complete relief.

 

As many patients receiving radiation therapy experience xerostomia, researchers around the world are testing different treatment methods. In this article, we’ll discuss recent developments in three areas of radiation-induced dry mouth treatment: gene therapy, cell therapy, and circular RNA therapy. 

 

Gene Therapy

Professor Stefano Fedele, Head of Clinical Research and Programme Director at UCL Eastman Dental Institute in the UK, is leading a new study, entitled AQUAx2, which is testing a new treatment for radiotherapy-induced dry mouth. 

 

The trial involves gene therapy that uses a viral vector to deliver a specific gene to damaged salivary glands. This gene helps the glands transport water into the mouth. While it can’t heal the damaged salivary glands, transported water to the mouth can help restore moisture and reduce uncomfortable, and often painful, dry mouth symptoms. 

 

Cell Therapy

Radiation treatment damages the acinar cells in the salivary glands, which are responsible for producing saliva, as well as salivary gland adult stem cells, which are the source of replenishing salivary gland tissue. 

 

Autologous mesenchymal stromal cells (MSCs) are a promising cell-based therapy that enables the healing and rejuvenating of adult stem cells. Researchers at the University of Wisconsin have studied autologous MSCs in mice models and have shown a 30% to 50% increase in salivary flow rate. Additional Danish research has shown promising effects in recouping salivary function in patients with radiation-induced xerostomia through autologous MSCs.

 

Further research on the subject is taking place in a phase 1 pilot and clinical trial at the University of Wisconsin, which will examine the use of autologous bone marrow–derived MSCs for treatment of radiation- induced xerostomia.

 

Whereas prior studies focused on treating chronic radiation-induced xerostomia, the clinical study at the University of Wisconsin will attempt to prevent it. In the first in-human trial of its kind, researchers will transplant autologous MSCs derived from a minor salivary gland, which will be expanded, prelicensed with interferon gamma and TNF-α, and cryopreserved. Patients will be followed closely for several months with researchers recording safety/tolerability, salivary production, and quality of life. 

 

Circular RNA Therapy

Head and neck cancer have become the sixth most common malignant tumor, and they are often treated by radiation therapy, which, in turn, damages the salivary glands and results in dry mouth and/or hyposalivation. 

 

In a first, the FDA recently cleared an IND (Investigational New Drug) application for the Phase I/IIa Study of RXRG001, a circular RNA therapy in development by the biopharmaceutical company RiboX Therapeutics Ltd. 

 

The study will evaluate the safety and efficacy of RXRG001, a proprietary RNA technology, in patients with radiation-induced dry mouth and hyposalivation. RXRG001 consists of the circular RNA coding human aquaporin 1 (a water channel protein of cell membrane), encapsulated in lipid nanoparticles. It is designed to increase saliva production by restoring water permeability via overexpression of human aquaporin 1, thereby alleviating dry mouth symptoms. 

 

Non-clinical studies have already demonstrated a favorable risk and benefit profile of RXRG001 in animal models. This new study hopes to shed light on its efficacy in human patients. 

 

Bonus: Electrostimulation Therapy

Intraoral electrostimulation is a dry mouth treatment technique that can be used for radiation-induced xerostomia and xerostomia brought on by other causes, such as illness or medication. Intraoral electrostimulation delivers small electrical impulses to the oral cavity, which stimulate the salivary glands to naturally produce more saliva. 

 

If the salivary glands are extremely damaged, electrostimulation might not be effective, as there is no mechanism to be stimulated. If, however, the salivary glands are partially damaged, electrostimulation may be exactly the boost they need to improve their function. 

 

As always, people with radiation-induced xerostomia should check with their medical providers about whether intraoral electrostimulation should be included as part of their comprehensive dry mouth treatment plan. Typically, treatment plans include more than one method, which maximizes the chances of success. 

 

FAQS

What is xerostomia?

Xerostomia is the subjective feeling of dry mouth, and occurs when the salivary glands cease to function properly. This can be due to radiation therapy for head and neck cancer, disease like diabetes or Sjrogren’s syndrome, or medication that causes dry mouth as a side effect. 

 

Without sufficient saliva, both oral health and general health can quickly deteriorate, resulting in increased dental caries and infections, difficulty chewing, swallowing, and talking, halitosis, change in taste, sore throat, and more. The combination of these dry mouth symptoms can significantly diminish patients’ quality of life. 

 

Why is research about radiation-induced xerostomia important?

This type of research is important because radiation treatment for head and neck cancers cause xerostomia in anywhere between 40% and 80% of those treated. This is a pervasive problem among those being treated for these types of cancer, and its symptoms can directly decrease patients’ quality of life. 

 

Is radiation the only cause of xerostomia?

No, xerostomia can be caused by radiation, as well as a host of other things, such as illness (Sjogren’s syndrome, diabetes, thyroid disease), medication, stress, and more. 

 

Is xerostomia treatment dangerous?

The current methods being researched for xerostomia treatment undergo rigorous testing, which means that they will only be FDA-approved if they are safe. Of course, many treatments have unpleasant side effects, which are different from actual risk. Intraoral electrostimulation, however, is one xerostomia that has been proven safe and has no unpleasant side effects. 

 

How does intraoral electrostimulation work as a xerostomia treatment?

Intraoral electrostimulation delivers small electrical impulses to the oral cavity, which stimulate the salivary glands to naturally produce more saliva. The impulses are delivered via a small handheld device that people can use at home. The benefit of this treatment is that there are no pharmacological side effects, as is the case with medication used to treat xerostomia. 

 

Where can I learn more about electrostimulation for xerostomia?

You can learn more about electrostimulation for xerostomia on the Saliwell website. Saliwell is the producer of the Salipen, an FDA-approved handheld device for intraoral electrostimulation.