Rheumatologist Aleksander Lenert, MD, MS, FRCPC, recently received a five-year, mentored, and patient-oriented K23 research career development award in the amount of $837,000 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) entitled, “Investigating Disease Activity, Bone Damage and Interleukin-1 Genes in Adult SAPHO Syndrome and Chronic Nonbacterial Osteomyelitis.” The research will focus on adults with synovitis acne pustulosis hyperostosis osteitis syndrome and chronic nonbacterial osteomyelitis (SAPHO-CNO), a rare autoinflammatory disease primarily targeting bones and joints and currently without any FDA-approved therapies.

“As an aspiring junior clinical investigator, I am honored to be a recipient of this competitive NIH-funded award,” Lenert said. He will lead a unique prospective observational study in adult SAPHO-CNO “to address critical knowledge gaps about disease activity assessments, risk factors for severe outcomes, and influence of variants in IL-1 pathway genes on clinical phenotypes in adults.”

Pediatric rheumatologist Polly Ferguson, MD, will serve as Lenert’s mentor on the project. The Marjorie K. Lamb Professor of Pediatrics is the world-leading expert in CNO, and serves as the Division Director of Pediatric Rheumatology, Allergy and Immunology in the University of Iowa Stead Family Department of Pediatrics.

Ferguson sees Lenert’s work as being synergistic with the work her lab is doing, as well as with the efforts of pediatric rheumatologists around the world to better understand pediatric CNO. They both are working with the goal in mind of FDA-approved treatment options for both pediatric and adult patients who have the syndrome.

“Very little is known about SAPHO-CNO,” Ferguson said. “There are long diagnostic delays, no diagnostic tests and very limited information on long-term outcomes and even less on the impact of the disease on the patient. His work fills a critical gap in the field and will be highly impactful. Dr. Lenert has put in the hard work to get an adult registry established, assembled a terrific mentoring group, and wrote an outstanding K proposal that was funded on the first submission! He has made my job as his primary mentor pretty easy.”

Lenert’s internal mentoring team also includes Mary Vaughan-Sarrazin, PhD, Associate Professor of Internal Medicine and Director of the Biostatistics and Data Analysis Core in the Carver College of Medicine’s Program in Population Health; and the College of Education’s Professor and E. F. Lindquist Chair in the Department of Psychological and Quantitative Foundations, Jonathan Templin, PhD.

The SAPHO-CNO Study seeks to improve clinicians’ understanding of patient-reported symptoms, such as musculoskeletal pain, fatigue, and other important quality of life domains, and studying the use of advanced imaging with whole-body magnetic resonance imaging (MRI) in clinical disease activity assessments.

“I will also try to identify potentially modifiable factors and symptom groups that are predictive of developing severe bone damage,” Lenert said. “Finally, I am interested in the potential discovery of mutations in inflammatory pathway genes of adults with SAPHO-CNO, which may shed light on the spectrum of disease symptoms and complications in SAPHO-CNO.”

The findings from this K23 project could be used to guide future clinical trials in testing different treatment strategies in adult patients by targeting subgroups of patients who many benefit from earlier and more aggressive treatment, in turn, promoting higher success rates in patient outcomes.

“Future research directions stemming from this work include the development and validation of a patient-reported disease activity tool for use in the clinic, identification of novel biomarkers for earlier diagnosis, and deepening our understanding of long-term disease complications and responses to treatment, all of which would directly benefit adults with SAPHO-CNO,” Lenert said.

He continued:

I am so proud and honored to be a faculty at the University of Iowa! Our institution is truly a unique place in the country, which has given me the opportunity to grow my passion in the clinical care and research of adults with rare rheumatic diseases such as SAPHO-CNO. I am very thankful for the unwavering support of my family, specifically from my wife, Lindsay, my children, Niko and Ella, and my parents Petar and Gordana, who are always by my side, and make my life complete. In addition to my family’s commitment to my career as a rheumatologist and clinical researcher, I have to thank my former chief of the Division of Immunology, Dr. Scott Vogelgesang, who recruited me to Iowa in late 2019 and provided me with the necessary support and environment to grow my passion in clinical research in rare rheumatic diseases. With ongoing support from my current chief, Dr. Ben Davis, the Department of Internal Medicine, and the institution, I look forward to building on my K23 project towards developing a strong and collaborative clinical and translational research program within the Division of Immunology here in Iowa.

Lenert also offered his gratitude to his full mentoring team and collaborators:

• Associate Professor of Pediatrics-Medical Genetics and Genomics, Associate Director of the Iowa Institute of Human Genetics, University of Iowa, Benjamin Darbro, MD, PhD
• Associate Professor of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Robyn Domsic, MD, MPH
• Professor of Pediatrics-Medical Genetics and Genomics, Division Director of Medical Genetics and Genomics, University of Iowa, Hatem El-Shanti, MD
• Associate Professor of Radiology, University of Iowa, Takashi Shawn Sato, MD
• Professor of Medicine at Harvard Medical School, Chief of the Section of Clinical Sciences in the Division of Rheumatology, Inflammation and Immunity at Brigham and Women’s Hospital, Daniel Solomon, MD, MPH
• Associate Professor of Pediatrics, Seattle Children’s Hospital/University of Washington, Yongdong Zhao, MD, PhD, RhMSUS
• Assistant Professor of Medicine, Hospital for Special Surgery, Karmela Kim Chan, MD