Researchers have made an exciting breakthrough in understanding calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout.
This condition is a type of arthritis caused by the buildup of tiny calcium crystals in the joints. It affects many older adults, especially those over 60, and can cause painful joint swelling and long-term joint damage.
Right now, there are no targeted treatments available—doctors usually treat the symptoms with pain relievers or anti-inflammatory medications.
In a new study published in the Annals of the Rheumatic Diseases, scientists identified two genes, ENPP1 and RNF144B, that contribute to the development of CPPD disease. This marks the first time a genome-wide association study (GWAS) has been done to find genetic causes of CPPD.
The researchers used data from over 550,000 people—mostly male veterans—from the Million Veterans Program in the United States. These participants had either African or European ancestry, and the same two genes showed up as risk factors in both groups.
The most important discovery was the gene ENPP1. This gene makes a protein that produces substances called adenosine monophosphate and inorganic pyrophosphate. When these substances combine with calcium, they can form the crystals that lead to CPPD. So, it makes perfect sense that ENPP1 would be involved in this disease.
Doctors are especially excited because there are already drugs developed for other conditions, such as infections and cancer, that target this protein. These medications could now be tested as possible treatments for people with CPPD.
The second gene, RNF144B, is less understood, but scientists believe it may play a role in the body’s inflammation response.
Inflammation is a major problem in CPPD disease, especially during a flare-up, when joints become swollen, red, and very painful. The identification of RNF144B opens the door for new research into how this gene might be involved in joint inflammation.
CPPD disease often appears on X-rays as a condition called chondrocalcinosis, which shows calcium buildup in the cartilage.
About 10% of middle-aged adults in Europe and North America show signs of this disease, and the number increases to nearly 30% in people over 80. While it’s still not clear whether CPPD causes osteoarthritis or results from it, the two are often linked.
Acute cases of CPPD, sometimes called pseudogout, occur when calcium crystals trigger inflammation in the joint. The body responds by releasing a chemical called IL-1b, which causes pain and swelling.
This sudden inflammation can feel a lot like a gout attack, which is why it’s been called pseudogout. But unlike gout, which is caused by uric acid crystals, CPPD involves calcium pyrophosphate crystals.
Dr. Tony Merriman, the lead scientist on the project, says this discovery was a ‘eureka moment’ in his career. He is excited about the potential to turn this finding into new treatments that could really help patients.
Dr. Sara Tedeschi, a rheumatologist and co-author of the study, adds that it’s very promising because ENPP1 is directly involved in producing the crystal-building material—making it a clear target for future therapy.
Currently, treatments focus on reducing inflammation using drugs like NSAIDs, colchicine, or prednisone. But these do not stop the crystals from forming. With the discovery of ENPP1 and RNF144B, researchers now have specific targets that could be used to develop drugs that address the root cause of the disease, not just the symptoms.
This research gives hope to millions of people, especially older adults, who suffer from painful joint problems due to CPPD. If clinical trials confirm the effectiveness of drugs targeting ENPP1, it could lead to the first truly targeted treatment for this overlooked but common form of arthritis.
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The study is published in Annals of the Rheumatic Diseases.
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