02/19/2026
A new study led by Riley Children’s Health and Indiana University School of Medicine physician-scientists has uncovered a promising therapeutic approach aimed at improving the neurobehavioral symptoms of neurofibromatosis type 1 (NF1).
NF1 is caused by changes in the gene that produces neurofibromin, a protein that regulates cell growth and processes in the brain. Those affected by NF1 (approximately 1 in 3,000 people worldwide) produce reduced levels of neurofibromin due to a mutation in one copy of the gene. While NF1 is well known for causing nerve tumors, reduced neurofibromin levels can also disrupt brain development and function.
The study is co-authored by Steven P. Angus, PhD, a researcher in the Herman B Wells Center for Pediatric Research, D. Wade Clapp, MD, chair of the Indiana University School of Medicine Department of Pediatrics, and Steven D. Rhodes, MD, PhD, hematologist-oncologist. The team’s work, published in the Journal of Clinical Investigation, demonstrates that stabilizing the protein neurofibromin can correct behaviors linked to ADHD and autism spectrum disorder, which are experienced by 50–70% of children with NF1.
Children with NF1 who experience neurobehavioral challenges currently have no treatment options specifically designed for their condition beyond standard medication. The team’s goal is to begin developing therapeutic approaches that directly address these unmet needs
The research team identified that reducing the breakdown of neurofibromin allowed mice with NF1 to regain more normal levels of the protein. This restoration corrected hyperactivity, impulsivity, and deficits in social learning by reducing abnormal brain signaling. Because this strategy addresses haploinsufficiency, the mechanism that drives NF1 and many similar disorders, the researchers believe it may be applicable to as many as 700 rare genetic conditions, significantly broadening its impact.
Looking ahead, the research team will focus on identifying drug candidates that increase functional protein levels while continuing to develop safe and effective delivery strategies to support future human studies. The findings offer new optimism and position Riley Children’s as a leader in moving NF1 care beyond symptom management and toward disease-modifying therapies.
Learn more
Check out the latest Riley Children’s Health annual report for more information about treatment, programs, novel procedures and research.
