Background
Decreased salivation and dry mouth are common complaints in the population and most often are caused by side-effects of drugs, but also by irradiation against salivary glands, or diseases in salivary glands. The frequency of dry mouth increases with age, mainly due to greater morbidity and drug use in the elderly population. Very low salivary secretion can impair oral health in the form of dental decay and wear, fungal infections, damage to the mucous membranes, difficulties with speaking and swallowing, and reduced general and oral-health related quality of life.
pSS is an autoimmune connective tissue disorder that mainly affects women from approximately 50 years of age. pSS involves dry mouth, dryness of the eyes, fatigue, pain in muscles and joints, significantly impaired quality of life and increased morbidity. The disease is the subject of great attention among clinicians and researchers; nevertheless, the cause is unknown.
It is of significant interest to the individual patient and to the patient group as a whole to achieve improved diagnostics and, thus, possible therapies.
Main goals of the research
To improve the situation for all groups of patients suffering from dry mouth symptoms and problems, through increased clinical awareness, accurate diagnosis, and better treatment
Specific sub-aims
- To characterize various dry mouth patient groups in detail
- To elucidate biomarkers for pSS using advanced investigations of tears, saliva and salivary glands from pSS patients
- To develop a nanomedicine-based product to alleviate the subjective feeling of dry mouth
Sub aim 1: To characterize various dry mouth patient groups in detail
Since our initial emphasis was on the pSS patients and they are bothered by dry mouth and dry eyes, we immediately started a collaboration with the Dry Eye Clinic, see below. Thus, it rapidly became our niche to evaluate the clinical characteristics of the oral cavity and the ocular surface as well as to apply proteomics, lipidomics, cytokine analysis and metabolomics to saliva and tears of various patient groups. Our work has resulted in numerous publications.
The Dry Mouth Clinic
The establishment of the Dry Mouth Clinic is an essential element of the overall project. During the fall of 2015, the Dry Mouth Clinic was established at the Institute of Clinical Dentistry through collaboration between resource persons from the departments of surgery, conservative dentistry and gerodontology.
The original members of the Dry Mouth Clinic were:
- Janicke Liaaen Jensen, project leader, Professor
- Bente Brokstad Herlofson, Professor
- Morten Rykke, Professor
- Alix Young Vik, Professor
- Lene Hystad Hove, Associate Professor
- Preet Bano Singh, Postdoc (now Associate Professor)
- Lara Aqrawi, Associate Professor
- Xiangjun Chen, Postdoc
- Shermin Rusthen, PhD candidate
- Bek Tashbajev, PhD candidate
- Håvard Hynne, PhD candidate (from 2018)
- Julie Frigaard, PhD candidate (from 2020)
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Ingrid Beate Ringstad, PhD candidate (from 2022)
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Tanya Cross, PhD candidate (from 2022)
Patients and clinical examinations
- pSS patients were identified partly in the Norwegian Systemic Connective Tissue Disease and Vasculitis Register (NOSVAR), the National Hospital, led by Øyvind Palm. Others were recruited among patients referred to the project leader (JLJ) for salivary gland biopsies see sub-aim 2.
- Patients with sicca symptoms and findings not fulfilling pSS-criteria (non-SS) and healthy age- and gender-matched controls were recruited at the Faculty of Dentistry
- Radiated head and neck cancer (HNC) patients were recruited from the National Hospital with the assistance of Professor Bente Brokstad Herlofson
- Medicated psychiatric patients were recruited from Lovisenberg Diaconal Hospital
- 65-year-old inhabitants of Oslo were recruited from the OsloMunn65-study which is a large study led by associate Professor Lene Hystad Hove
- Covid-19 patients were recruited through the CovidOral study on oral late effects in Covid-19 led by associate Professor Preet Bano Singh
All patients and controls were subjected to questionnaires on general and oral quality of life, as well as xerostomia. Patient history data were collected, oral mucosa and teeth were closely examined, saliva was collected, and tests on smell and taste were performed. Most participants were examined at the Dry Eye Clinic where the ocular surface was extensively evaluated, and tears collected.
In January 2023, a new project on oral and general health in acutely hospitalized old people was started. See The COOP-II-Study. Cooperation for better treatment of polypharmacy in the community.
External collaborators and analyses of saliva and tears
The Dry Eye Clinic, led by Tor Paaske Utheim, is the Nordic region's only special clinic dedicated to the diagnosis and treatment of dry eyes and performs advanced examinations of eyes and tears. In collaboration with Oslo University Hospital and the Department of Biosciences, saliva and tears were closely analyzed by size exclusion chromatography and proteomics. Cytokine analyses and metabolomics of saliva and tears were carried out at Department of Medical Biochemistry, Oslo University Hospital, and lipidomics at VITAS Analytical Services.
PhD defences within the project
In 2020, two PhD-theses were defended based on papers within the project, namely by Shermin Rusthen and Bek Tashbayev.
PhD candidate Håvard Hynne worked mainly on HNC patients and advanced biochemical analyses of saliva and tears that also were compared to findings in patients with pSS. He defended his thesis in 2022.
Sub aim 2: To elucidate biomarkers for pSS using advanced investigations of tears, saliva and salivary glands from pSS patients
The approach is to use various omics analyses on saliva and tear samples from pSS and non-SS sicca patients and healthy controls and then further explore the findings in salivary gland biopsies.
The project leader (JLJ) has for years performed salivary gland biopsies for pSS diagnostics. These biopsies are described by Professor Kathrine Skarstein at Haukeland Hospital. Histopathological evaluations were performed on formalin-fixed paraffin-embedded tissue samples and subjected to various immunohistochemical identification techniques in her lab as well as in the lab of Professor Maria Kukuruzinska at Boston University. mRNA expression was verified using reverse transcription quantitative real-time polymerase chain reaction in Professor Hilde Galtung’s lab at IOB. We recently started using RNAscope® in situ hybridization at Haukeland Hospital, a new technique to visualize molecules in specific cellular locations.
The biopsy material is now stratified into subgroups based on autoantibody positivity and degree of focal infiltration. Our combined efforts strive to identify salivary biomarkers for patient subgroups possibly yielding access to future personalized medicine. Two PhD candidates are currently involved in this work, Ingrid Beate Ringstad at UiO and Hanne Borge at UiB.
Sub aim 3: To develop a nanomedicine-based product to alleviate the subjective feeling of dry mouth
In 2020, a project on innovative treatment options for dry mouth based on polymer-covered liposomes was initiated in collaboration with Professor Marianne Hiorth, School of Pharmacy with Julie Frigaard, dentist and bioengineer as a Ph.D. student. This project is partly funded by SPARK/UiO Life Sciences.
The product, called Liposal, is currently under review by The Norwegian Medicines Agency and can hopefully be tested out at the end of 2023.
Contact information
Project leader Janicke Liaaen Jensen: jljensen@odont.uio.no