New Genetic Discoveries Offer Hope for CPPD Disease Treatment
Calcium pyrophosphate deposition (CPPD) disease,a common cause of acute inflammatory arthritis,notably in older adults,may soon have more effective treatment options thanks to a recent genome-wide association study (GWAS). The study, conducted within the Million Veterans Program, identified two genes – RNF144B and ENPP1 – strongly linked to the development of CPPD disease in both individuals of European and African ancestry.CPPD disease is triggered by the formation of calcium pyrophosphate (CPP) crystals within joints. These crystals activate the immune system, leading to the release of inflammatory molecules like IL-1B and resulting in painful, acute arthritis. A radiographic sign of the disease, condrocalcinosis, becomes increasingly prevalent with age, doubling in frequency each decade after 60.Currently, treatment focuses on managing inflammation with medications like non-steroidal anti-inflammatories (NSAIDs) or prednisone, but effective disease-modifying therapies are lacking – a important unmet need for patients.
The research team, led by Tony R.Merriman of the University of Alabama at Birmingham, the Birmingham VA Health System, and the University of Otago (New Zealand), focused on identifying genetic factors contributing to CPPD disease. the GWAS analyzed genetic data from over 550,000 veterans (91% male).
The revelation of ENPP1 is particularly significant. This gene encodes a protein that regulates the production of adenosine and inorganic pyrophosphate – key components that interact with calcium ions to form CPP crystals. Sara K. Germans, a co-investigator from Brigham and Women’s Hospital and Harvard Medical School, highlighted the logical connection: “The ENPP1 generates inorganic pyrophosphate, one of the components of the CPPs.” This finding suggests that inhibiting ENPP1 could be a promising therapeutic strategy.
While less is known about RNF144B,it is believed to play a role in inflammation. Importantly, existing drugs targeting ENPP1, originally developed for infectious diseases and cancer, could potentially be repurposed for CPPD treatment.
Dr. Josef Smolen, editor-in-chief of Annals of the Rheumatic Diseases, emphasized the importance of this first GWAS study in CPPD disease, stating it identifies “two goals for future treatments.”
Dr. Merriman concluded, “We are excited about the potential impact of what we have discovered…and the possibility of developing new drugs for the treatment of CPPD disease.” The research team describes the findings as an “Eureka Moment” with the potential to significantly improve treatment options for those suffering from this debilitating condition.Disclaimer: Consalud’s content is prepared by health specialized journalists and endorsed by a top-level expert committee. Though, we recommend that the reader consult a healthcare professional for any health-related concerns.
