Dr. Sheri Yang, Collaborator Awarded $2.79M to Advance Study, Treatment of Rheumatoid Arthritis
Dr. Sheri Yang
Philadelphia – Penn Dental Medicine’s Dr. Shuying (Sheri) Yang, Professor in the Department of Basic & Translational Sciences, and collaborator Dr. Michael Mitchell, Associate Professor of Bioengineering at Penn Engineering, have been awarded a $2.79M grant (over five years) from the National Institutes of Health (NIH) to study a possible new treatment for rheumatoid arthritis (RA). Their collaboration was catalyzed by the School’s Center for Innovation & Precision Dentistry (CiPD), a joint center with Penn Engineering.
Affecting approximately 1% of the global population, RA is a severe autoimmune disorder that leads to chronic pain, inflammation, and joint destruction. Current treatments often fall short, with reportedly up to 40% of patients failing to respond effectively, while biologic therapies leave 6-21% of patients resistant to treatment.
“There is an urgent need for more effective treatments that target the underlying mechanisms of RA,” says Yang. “Our research focuses on the critical role of Inositol polyphosphate-5-phosphatase E (INPP5E), a 5-phosphatase that plays significant physiological roles in embryonic development, neurological function, the immune system, and blood cell proliferation and function.”
To date, their findings reveal that INPP5E expression is significantly reduced in the cells that play a pivotal role in RA pathogenesis. Through cutting-edge mouse models, we have demonstrated that overexpression of INPP5E in macrophages reduces inflammation and bone destruction, suggesting that INPP5E is a potential internal protector against RA.
The innovative aspect of their project lies in the development of a novel delivery system using lipid nanoparticles (LNPs), enabling targeted delivery of INPP5E mRNA specifically to cells in the lining and sub-lining tissue of joints. “This approach offers a breakthrough in RA treatment by enhancing precision in drug delivery and maximizing anti-inflammatory effects,” explains Yang. “Our targeted mRNA therapy not only inhibits key inflammatory pathways, but also mitigates bone erosion, presenting a dual therapeutic benefit.”
By bridging molecular insights and innovative drug delivery technologies, this project aims to transform the landscape of RA management and holds significant promise for advancing RA treatment, offering a novel therapeutic strategy that could lead to more effective, targeted interventions for patients who do not respond to current therapies.