Discovery of genes relevant to disease a ‘eureka moment'
Treatment for calcium pyrophosphate deposition (CPPD) disease — more commonly known as inflammatory arthritis — may soon take a major step forward following a major discovery by a University of Otago researcher.
There is an unmet need for treatment of CPPD disease, which focuses on the alleviation of inflammation with non-steroidal anti-inflammatory drugs.
But University of Otago microbiologist and immunologist Dr Tony Merriman has led an analysis of the genes of 550,000 Americans with the disease, while based at the University of Alabama, Birmingham.
It is a first-of-its-kind genome-wide association study into the disease and the research found two genes — RNF144B and ENPP1 — that cause the debilitating calcium pyrophosphate crystal deposits in joints.
He said the genes were detected both in people of European ancestry and African ancestry.
"The most significant result of our research was the discovery of one of the genes, ENPP1.
"The protein encoded by this gene controls the production of chemicals — adenosine monophosphate and inorganic pyrophosphate — that, together with calcium ions, lead to the formation of the CPP crystals," Dr Merriman said.
Little is known about the other gene — RNF144B — aside from the possibility it is involved in inflammation.
More was known about ENPP1 and of its potential importance to people with CPPD disease.
Drugs targeting the protein have been developed in the treatment of infectious disease and cancer and they could now be evaluated for the treatment of CPPD disease.
Dr Merriman said the discovery opened up promising new avenues for targeted prevention and treatment of CPPD disease, which were lacking at present.
Co-investigator and Brigham and Women's Hospital rheumatology, inflammation and immunity division researcher Dr Sara Tedeschi said the genome-wide association with ENPP1 was "particularly exciting" as a rheumatologist because "it makes sense".
"ENPP1 generates inorganic pyrophosphate, one of the components of CPP crystals.
"Patients with CPPD disease are desperate for an effective treatment and trials testing ENPP1 inhibitors in CPPD disease would be of great interest."
Dr Merriman said the researchers were "thrilled" about the potential impact of their discovery and the possibility of new drugs being developed for the treatment of CPPD disease.
"The findings of this study produced a 'eureka moment', which can be rare in a scientist's career."
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