NIDCR Prepares First-in-Human Trial for Jansen’s Disease Therapy

Nearly 10,000 rare diseases collectively affect an estimated 25 to 30 million people in the United States. Yet treatments exist for only a small fraction of them, in part because the diseases are often too rare to attract major pharmaceutical investment. NIH is uniquely situated to address these challenges.

One example is Jansen's metaphyseal chondrodysplasia, also known as Jansen’s disease, an ultra-rare genetic condition that disrupts normal bone development starting in infancy. Just 30 people worldwide are known to have Jansen’s disease, which can cause severe skeletal abnormalities, chronic pain, and mobility problems. Many patients also experience significant complications affecting the skull, jaw, and facial bones, which can lead to significant dentofacial differences as well as hearing and vision loss. There are no effective treatments for Jansen’s disease, and patients typically need frequent surgeries over a lifetime.

Now, NIDCR researchers are preparing to launch a first-in-human clinical trial of an experimental drug designed to correct the molecular defect that drives the disease. The study represents a major milestone, not only for families affected by Jansen’s disease, but also for NIH’s broader efforts to advance treatments for rare and neglected diseases that might otherwise go unstudied.

“This is exactly the kind of challenge NIH’s intramural research program is uniquely positioned to take on,” said NIDCR Clinical Director Janice Lee, D.D.S., M.D., M.S. “Rare pediatric bone diseases require highly specialized expertise, long-term commitment, and close collaboration across many groups.”

Dr. Lee said NIDCR’s experience studying rare skeletal diseases in children made the institute especially well-suited to lead the trial. NIDCR has deep expertise in metabolic bone disorders like Jansen’s disease, particularly those involving the skull and face. Metabolic bone disorders typically arise from deficiencies in bone-strengthening minerals or hormonal imbalances.

The study will be led by Alison Boyce, M.D., a pediatric endocrinologist who heads NIDCR’s Metabolic Bone Disorders Unit. For over a decade, she has led a clinical study at NIDCR to understand the nature and course of another rare metabolic bone disorder called fibrous dysplasia/McCune-Albright syndrome, or FD/MAS. Insights from that longstanding study enabled Dr. Boyce, in recent years, to launch clinical trials in adults and children that demonstrated the promise of two different drugs in improving bone quality and strength in FD/MAS.

The upcoming Jansen’s trial is the result of years of collaboration across NIH and beyond. Scientists at Massachusetts General Hospital developed the experimental compound, which is designed to switch off the overactive protein that underlies the disease. NIH’s National Center for Advancing Translational Sciences teamed with the Massachusetts General scientists to speed preclinical studies required by the U.S. Food and Drug Administration before an experimental drug can be tested in humans. At the same time, clinician-scientists at NIDCR, the National Institute of Diabetes and Digestive and Kidney Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Cancer Institute contributed key clinical expertise to help advance the project into human studies.

“This work demonstrates how NIH’s collaborative structure allows multiple institutes and centers to combine expertise in ways rarely possible elsewhere,” said Dr. Boyce. “There probably wouldn’t be a first-in-human trial in Jansen’s disease without a program like this.”

Patient advocates have also been central to the effort from the beginning. Families affected by Jansen’s disease worked closely with researchers to drive momentum for the project from the very beginning. According to Dr. Boyce, NIH’s and NIDCR’s longstanding partnerships with patient advocacy organizations have been critical to advancing research in rare skeletal diseases.

For families living with Jansen’s disease, the upcoming study represents more than a scientific achievement. It offers hope that a condition long considered untreatable may finally have a targeted therapy on the horizon, and it highlights the unique role NIH can play in bringing treatments to patients with even the rarest diseases.

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