Study links measles virus and Paget’s disease

A team of investigators has confirmed a that the measles virus plays a key role in the development of Paget’s disease.

G. David Roodman, MD, PhD, an investigator of the study noted in a University of Pittsburgh press release that the drop seen in prevalence of Paget’s disease in the past 25 years could reflect the impact of the measles vaccination on the disease or that another environmental factor involved in Paget’s disease has changed.

Roodman and colleagues sought to understand the roles of mutations in the p62 gene, which is common among those with Paget’s disease, and the measles virus nucleocapsid protein (MVNP) by examining the affected and unaffected bone marrow of 12 patients with Paget’s disease and eight individuals without the disease. The investigators also bred and studied mice with the p62 mutation and MVNP.

“Our earlier work showed that bone cells called osteoclasts in about 70% of these patients contain [MVNP],” Roodman stated in the release. “Also, when we engineered normal osteoclasts in mice to contain, or express the measles protein, pagetic bone lesions formed.”

In their recent study, investigators found that marrow from eight patients with Paget’s disease expressed MVNP; three of them expressed MVNP in both affected and unaffected bone sites. In test tube experiments, osteoclast precursor cells from patients with Paget’s disease who made MVNP formed pagetic osteoclasts and displayed other typical Paget’s disease responses, according to the release.

By comparison, osteoclasts from the four patients who did not make MVNP appeared normal.

“It’s not clear why this would happen,” Roodman stated in the release. “It could be that other viruses or genes are triggering Paget’s disease in these patients.”

Reference:
Kurihara N. Cell Metab. 2011;13(1):23-34.
Disclosure: The study was funded by the National Institutes of Health and the Paget’s Foundation.

Paget's disease remains an enigmatic disorder. Our understanding of its etiology is still incomplete, but since the discovery that many patients with familial Paget's disease have SQSTM mutations, genetic theories have been dominant. Other evidence, in particular the decline in disease prevalence and severity, suggests that there are important environmental determinants too. One potential factor is the measles virus.

Kurihara and colleagues report persuasive data on the interaction between measles virus nucleocapsid protein (MVNP) gene expression and the common SQSTM1 mutation P392L (or its murine equivalent) on the in vitro behavior of osteoclasts. Their conclusions support the view that SQSTM1 mutations alone may not be sufficient to cause Paget's disease. As the authors acknowledge, the story is not complete: not all the patients in the study expressed MVNP in their marrow cells, and it is not clear that the murine model recapitulates all the features of the human disease.

— Tim Cundy, MD
Professor of Medicine University of Auckland
Aotearoa, New Zealand

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