Sjögren’s syndrome is a chronic autoimmune disease primarily affecting moisture-producing glands, such as those for tears and saliva. This leads to persistent dry eyes and dry mouth, significantly impacting quality of life. The syndrome can also have systemic effects, affecting various organs. While there is currently no cure, research is developing new treatments to manage symptoms and address underlying disease processes.
Understanding Sjögren’s Syndrome
Sjögren’s syndrome is characterized by the immune system mistakenly attacking healthy tissues, particularly the lacrimal (tear) and salivary glands. This autoimmune attack leads to inflammation and damage within these glands, reducing their ability to produce sufficient moisture. Patients frequently experience severe dry eyes and mouth, which can cause discomfort, difficulty eating, speaking, and an increased risk of dental problems and eye infections.
The disease can extend beyond the glands, potentially affecting joints, skin, lungs, kidneys, and the nervous system, leading to symptoms such as joint pain, fatigue, and skin rashes. Current standard treatments often focus on alleviating these symptoms, for instance, with artificial tears or saliva substitutes. However, these approaches do not address the root cause of the disease, underscoring the need for therapies that modify the disease course and offer comprehensive relief.
Immune System Targeted Therapies
New treatments focus on specific immune system components in Sjögren’s syndrome. Biological therapies, often monoclonal antibodies, target particular immune cells or signaling molecules. These therapies aim to modulate or suppress immune responses, reducing inflammation and slowing disease progression.
B-cell targeted therapies are a significant area of advancement, as B-cells play a role in Sjögren’s autoimmune response. Medications like rituximab, for example, work by depleting CD20+ B-cells, a type of white blood cell involved in immune system activity. Studies indicate these therapies can reduce symptoms and improve patient well-being, offering an alternative for those not responding well to conventional treatments.
Cytokine inhibitors are another category of immune-targeting therapies under investigation. Cytokines are signaling proteins that regulate immune responses and contribute to inflammation in Sjögren’s syndrome. By blocking the activity of specific cytokines, such as TNF-alpha, IL-6, IL-17, or IL-12/23, these inhibitors aim to reduce the inflammatory processes that drive the disease. Clinical trials are evaluating the safety and effectiveness of these inhibitors, aiming to improve symptom management and potentially alter disease activity.
Other Emerging Treatment Approaches
Beyond immune system modulation, other strategies are being explored for Sjögren’s syndrome. Neurostimulation investigates how stimulating specific nerves can increase the production of tears and saliva. For instance, stimulating the sphenopalatine ganglion, a nerve cluster located behind the nose, has shown potential in early studies to alleviate dry eyes and mouth by promoting glandular secretion. This technique aims to provide relief for persistent dryness symptoms.
Salivary gland gene therapy focuses on delivering therapeutic genes directly to affected salivary glands. The goal is to restore normal gland function or enable the glands to produce beneficial proteins. While still in early stages, this approach holds promise for a more targeted and potentially long-lasting treatment by addressing moisture production issues.
Experimental cell therapy trials explore the use of a patient’s own enhanced stem cells to improve salivary gland function. In one clinical trial, cells extracted from a patient’s bone marrow are activated and then injected into the salivary glands. This approach aims to restore fundamental functions like saliva production for individuals with severe dry mouth due to Sjögren’s disease.
Promising Drugs in Clinical Trials
Several drug candidates are in advanced clinical trials, showing promise for Sjögren’s syndrome. One example is Dazodalibep (VAY736), an anti-CD40 ligand antibody. This drug blocks the interaction between CD40 and CD40L proteins, a pathway involved in activating B-cells and promoting immune responses. By inhibiting this interaction, Dazodalibep aims to reduce autoimmune activity in Sjögren’s syndrome.
Clinical trials show Dazodalibep can significantly reduce systemic disease activity and symptoms like dryness, fatigue, and pain. In a Phase 2 study, patients receiving Dazodalibep showed improvements in systemic disease activity and symptom reduction over 169 days. These positive outcomes suggest Dazodalibep may be the first new drug to address both the disease process and symptoms of Sjögren’s syndrome, though larger clinical trials are needed to confirm findings.