Discovery of new genetic links offers potential for the prevention and treatment of a common form of inflammatory arthritis.
A groundbreaking genetic study has identified two key genes linked to calcium pyrophosphate deposition (CPPD) disease, a painful and common form of inflammatory arthritis also known as pseudogout. Published in the Annals of the Rheumatic Diseases, this first-ever genome-wide association study (GWAS) highlights ENPP1 and RNF144B as major contributors to the development of CPPD in people of both European and African ancestry.
What Is CPPD Disease?
Calcium pyrophosphate deposition disease (CPPD) is a type of crystal-induced arthritis caused by the buildup of calcium pyrophosphate crystals in the joints. Often mistaken for gout, pseudogout leads to episodes of severe joint pain, inflammation, and swelling. CPPD is most common in adults over 60 and is seen in up to 30% of people over the age of 80.
In many cases, CPPD also coexists with osteoarthritis, and while the connection is not fully understood, the condition contributes significantly to joint damage and reduced mobility in older adults.
Key Findings: ENPP1 and RNF144B Identified as Genetic Drivers of CPPD
This large-scale genetic study was conducted through the Million Veteran Program, which includes health data from over 550,000 U.S. Veterans. Researchers analyzed every gene in the human genome to uncover genetic links to CPPD arthritis, and the results were clear: ENPP1 and RNF144B are strongly associated with the disease across multiple ethnic groups.
ENPP1 encodes a protein responsible for producing inorganic pyrophosphate, a critical component in CPP crystal formation.
RNF144B, though less understood, appears to play a role in inflammatory signaling pathways relevant to arthritis.
A Major Breakthrough in Understanding and Treating Pseudogout
Dr. Tony R. Merriman, lead researcher from the University of Alabama at Birmingham and University of Otago, explains:“Our discovery of ENPP1 is a game-changer. This gene directly impacts the chemical pathways that lead to CPP crystal buildup. It provides a clear and actionable target for new therapies.”
Dr. Sara K. Tedeschi, a rheumatologist at Harvard Medical School, adds:“This is an exciting time. ENPP1 inhibitors, already under development for other diseases, could be repurposed to finally offer an effective treatment for CPPD disease—something patients have needed for decades.”
Why This Study Matters: Unmet Need for CPPD Treatment
Currently, CPPD disease treatment options are limited to managing inflammation with NSAIDs, colchicine, or corticosteroids. There are no therapies that target the root cause—crystal formation.
Dr. Josef Smolen, Editor-in-Chief of Annals of the Rheumatic Diseases, emphasizes:“This landmark GWAS not only identifies potential drug targets but also brings us closer to precision medicine for inflammatory arthritis like pseudogout.”
What’s Next?
Because ENPP1 inhibitors are already in development for cancer and infectious diseases, they may soon be tested in clinical trials for CPPD arthritis. This could rapidly accelerate the timeline for delivering effective, disease-modifying treatments.
Key Takeaways for Patients and Healthcare Providers
CPPD (pseudogout) is a common inflammatory arthritis in older adults caused by calcium pyrophosphate crystals.
New genetic research identifies ENPP1 and RNF144B as key contributors.
ENPP1 inhibitors may represent a future treatment for CPPD disease.
Current CPPD treatments only manage symptoms, not the underlying cause.
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