Austrian researchers have discovered mutations in genes that regulate the metabolic sensor mTOR in patients with familial sarcoidosis, according to a study published in the European Respiratory Journal.

At the same time, a clinical trial is starting at MedUni Vienna’s Department of Dermatology to test the efficacy of mTOR inhibitors in the treatment of sarcoidosis.

Sarcoidosis is a disease in which nodules of immune cells form, primarily in the lungs but also in the skin or in the heart. While the lung symptoms are similar to those of tuberculosis, the etiology of the disease is unknown. It is currently assumed that causation is multifactorial, whereby certain environmental impacts and bacterial pathogens trigger sarcoidosis in genetically predisposed individuals. For example, there was a rise in the number of cases of sarcoidosis among fireman who were deployed during 9/11, due to the enormous dust burden to which they were exposed. Also, the bacterium responsible for causing acne is found in the pulmonary granulomas of many patients.

A research team has now identified a genetic component that is involved in development of the disease. By conducting a genome analysis of families in which there are clusters of sarcoidosis, the study shows that the metabolic sensor mTOR plays a central role in the pathogenesis of sarcoidosis. In addition to this, the exome, which is the coded portion of the genome, of 22 people from 5 families was sequenced.

“The unique thing about the study design was that it allowed us to analyze patients and their unaffected siblings over three generations in some families. In this way we were able to identify mutations that were passed on exclusively to patients but not to their healthy relatives,” said researcher Thomas Weichhart.

Following detailed bioinformatic analysis, it was found that many mutations relate to genes that normally deactivate the metabolic sensor mTOR. “The mutations then result in mTOR being more active, so that these nodules, so-called granulomas, are more readily able to form,” lead author Clarice Lim explained.

Researchers had already demonstrated in an animal model that the activation of mTOR in immune cells was sufficient to cause sarcoid granulomas to form. The new data now show that, on a genetic level as well, mTOR contributes to the development of sarcoidosis in patients.

MedUni Vienna’s Department of Dermatology is currently conducting a clinical trial to test a therapeutic application of this relationship. A study funded by the Vienna Science and Technology Fund (WWTF) is to investigate the efficacy of the mTOR inhibitor Sirolimus in sarcoidosis patients with skin and pulmonary involvement.

Sarcoidosis patients are still being sought for this clinical trial and an information event for patients will be held on 23 May 2019 starting at 18:30 hrs, with leading experts in sarcoidosis treatment and research at MedUni Vienna (interested parties should please email Georg Stary at [email protected]).