Veterans Affairs

Sarcoidosis animal model

Accurate model will enable research towards the development of therapeutics to this lethal disease

Medical & Biotechnology

This image shows granulomas that are mostly undergoing peripheral fibrosis. Some granulomas showing complete fibrous obliteration are present along the left margin. Image Credit: Yale Rosen on Flickr

Scientists at the VA have recently developed novel mouse models for sarcoidosis research and drug development. The patented technology is available via patent license agreement to companies that would make, use, or sell it commercially.

Sarcoidosis is a common condition in the U.S. population – especially African-Americans with a prevalence of 39 in 100,000 – and mostly affects adults aged 20-40 years old. The mortality rate for sarcoidosis is between 1% and
5% but more recent reports confirm that the rate of
hospitalization and death from sarcoidosis has increased
significantly during the past 30 years.

While the etiology of sarcoidosis remains unclear it is considered an airborne disease, at least in a subset of patients, since the lungs, eyes, and skin are the most affected organs. The possible environmental etiologies include exposure to dusts, microbe-rich environments, and chemical agents.

A major limitation in sarcoidosis research is the lack of an appropriate experimental animal model to mimic disease. As mentioned above, the etiology and pathogenesis of sarcoidosis is poorly understood and that limits effective modeling. However, the association of sarcoidosis with viral and bacterial antigens is well documented. Propionibacterium acnes and mycobacterial proteins are the most common antigens isolated from sarcoidosis lesions of the lung and antigen-specific immune responses to mycobacterial virulence factors have been found in bronchoalveolar lavage (BAL) samples from sarcoid patients.

Given the above evidence and need, VA researchers have developed animal models for lung sarcoidosis. The animal models have granulomas comprising Mycobacterium abscessus (MAB) cell wall particles. The model was enabled by the culturing of peripheral blood mononuclear cells with MAB. Samples were isolated from 9 patients with confirmed pulmonary sarcoidosis. The model will have utility:

  1. for screening compounds for therapeutic use in the treatment of sarcoidosis
  2. in assessing potential side effects of treatment of sarcoidosis
  3. for studying the mechanism of sarcoidosis, lung sarcoidosis, and/or one or more sarcoidosis-related symptoms

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