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The NIH Catalyst: A Publication About NIH Intramural Research

National Institutes of Health • Office of the Director | Volume 28 Issue 1 • January–February 2020

Recognizing 35 Years of Progress in Sjögren Syndrome Research

NIDCR Hosts a Special Grand Rounds to Celebrate

BY CATHERINE EVANS, NIDCR

Group photo

CREDIT: CHIA-CHI CHARLIE CHANG

The presenters at the “Celebrating 35 Years of Sjögren’s Syndrome Research at NIDCR” special grand rounds included (from left) Bruce Baum, Caroline Shiboski, Kathy Hammitt, Martha Somerman, Blake Warner, Janice Lee, and Steven Taylor.

Most of us know the parched sensation of dry mouth, whether from dehydration, side effects of medicine, nervousness, or something else. The dryness is usually fleeting, but not for people with Sjögren syndrome, an autoimmune disease that causes dry mouth and dry eyes. By attacking the salivary and tear glands, the syndrome interferes with taste, chewing, and swallowing, and it boosts the risk for cavities, tooth loss, and oral infections. Although there is not yet a cure for the syndrome, the symptoms can be treated.

In 1984, the National Institute of Dental and Craniofacial Research (NIDCR) established a clinic to evaluate people with salivary dysfunction and to better understand and find more effective treatments. To mark the clinic’s 35th anniversary, NIDCR hosted a special grand rounds in November 2019 to trace the past, present, and future of research on the condition. Today, clinical studies on dry mouth disorders and Sjögren syndrome continue in the NIDCR Dental Clinic in the Clinical Center.

NIDCR Director Martha Somerman introduced the first speaker, NIDCR Scientist Emeritus Bruce Baum, who along with Phil Fox established the first dry-mouth clinic in the United States. “Dr. Baum’s vision is why we’re here today,” Somerman said. “His pioneering work in the field, including the first-ever salivary-gland gene therapy tested in humans, helped build the groundwork for our current intramural and extramural research to understand and treat Sjögren’s syndrome.”

Salivary disorders such as Sjögren syndrome affect up to four million Americans, most of them women. The condition’s cause is unknown and it can significantly disrupt a person’s quality of life by interfering with the enjoyment of food and hindering speech. Soon after Baum’s arrival at NIDCR in 1982, he and Fox began seeing patients with salivary-gland disorders. In 1984, they established the NIDCR Dry Mouth Clinic, which later became the NIDCR Sjögren’s Syndrome Clinic. Their aim was to evaluate patients with dry mouth to better understand how Sjögren syndrome develops and to test treatments.

Their work led to the FDA approval of pilocarpine to prevent or treat dry mouth in people with Sjögren syndrome as well as dry mouth in people who have been treated with radiation therapy for head and neck cancer. This oral medication stimulates the salivary glands to make more saliva. Although the drug helps some people, not everyone finds relief.

“It’s so discouraging to see a patient and only be able to say, ‘There’s nothing I can do for you,’” Baum said.

So he turned to the idea of using a non-disease-causing virus to deliver a corrective gene directly into a damaged gland to restore the flow of saliva. In 2012, the results of the first trial in 11 humans with radiation-induced dry mouth showed that five participants had increased salivary flow that persisted in some cases for up to four years. A second trial using a slightly different viral delivery vehicle is ongoing, and Baum’s NIDCR successors, John Chiorini and Blake Warner, will soon launch a third trial to test the therapy’s efficacy in Sjögren syndrome.

Next, Kathy Hammitt, who has the syndrome and is a patient advocate and vice president of medical and scientific affairs at the Sjögren’s Syndrome Foundation, introduced the Foundation’s CEO, Steven Taylor. “For a long time, I felt like mine was one of the few voices in a dark space,” Hammitt said. “Steven Taylor brought in light when he arrived at the Sjögren’s Syndrome Foundation, which has grown exponentially over the last 16 years.

“Our vision is to create a community of patients, health-care professionals, and researchers to join together to conquer the complexities of understanding, diagnosing, and treating Sjögren’s,” said Taylor, who has been with the foundation since 2003.

The Sjögren’s Syndrome Foundation sponsors patient-support groups, raises awareness among the public and scientists, and funds research. These efforts have enabled successes such as shortening the time to diagnosis from six to just under three years. The Foundation’s ongoing efforts include drafting clinical-management guidelines for health-care professionals, leading discussions on developing biomarkers and novel diagnostics, formulating classification criteria, and engaging with the FDA on approval of therapies.

Caroline Shiboski, the Leland A. and Gladys K. Barber Distinguished Professor in Dentistry at the University of California at San Francisco, spoke next about her work since 2003 with the NIDCR-funded Sjögren’s International Collaborative Clinical Alliance (SICCA). The collaborative of nine research groups in seven countries has enrolled and evaluated more than 3,500 participants to develop a data and biospecimen registry and biorepository for the research community, as well as classification criteria for Sjögren syndrome.

“The heterogeneity of Sjögren’s syndrome, as well as the lack of effective systemic treatments, highlights the need for a personalized and targeted approach,” Shiboski said. Her group is proposing to perform transcriptomic analysis, in particular, single-cell mRNA sequencing, to identify disease subtypes and to search for biological targets for more effective therapies. The genetic information will be made available via the SICCA registry to scientists worldwide.

The final speaker was Blake Warner, who’s chief of NIDCR’s Salivary Disorders Unit, which conducts basic and clinical research. Understanding the syndrome is challenging, he said, because a “variety of pathological processes underlie a shared clinical presentation.”

Warner’s group works with a multidisciplinary team of experts in oral medicine, pathology, rheumatology, and ophthalmology to provide research-driven clinical assessments of patients with dry mouth. The aim is to solve questions about salivary-gland biology, autoimmunity, and treatment targets.

Recent work by Warner’s team to examine patients’ salivary-gland tissue revealed that the Janus kinase-signal transducers and activators of transcription (JAK-STAT) molecular-signaling pathway, which is implicated in autoimmunity, appears to be overactive in a subset of patients with Sjögren syndrome. Warner’s group will soon launch a clinical trial, at the NIH Clinical Center, to test an FDA-approved JAK-STAT inhibitor, tofacitinib, in Sjögren syndrome patients. (Tofacitinib is a product of John O’Shea’s lab in the National Institute of Arthritis and Musculoskeletal and Skin Diseases; see https://irp.nih.gov/catalyst/v25i1/innovations-john-o-shea-and-arthritis-drug.)

“As you’ve heard today, our progress over the past 35 years in understanding Sjögren’s syndrome couldn’t have been possible without collaborations among researchers, multiple NIH institutes and centers, and patients,” said NIDCR Clinical Director Janice Lee at the end of the program. “These partnerships will be critical as we look forward in coming years to the goal of better treatments and a cure.”


To watch a videocast of the “Celebrating 35 Years of Sjögren’s Syndrome Research at NIDCR” special grand rounds, held November 15, 2019, go to https://videocast.nih.gov/launch.asp?28871. For more information on the Sjögren Syndrome, visit https://www.nidcr.nih.gov/health-info/sjogrens-syndrome/more-info.

This page was last updated on Tuesday, March 29, 2022

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