Development of a Novel Human In Vitro Sarcoidosis Model
Study Details
Study Description
Brief Summary
There is currently no experimental model that accurately represents sarcoidosis. The lack of a useful research model significantly slows progress towards developing new treatments for sarcoidosis. The investigators plan to develop a new model for sarcoidosis research and will test the model to see if it helps us understand how sarcoidosis develops and if it is useful for testing new treatments.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Sarcoidosis is a systemic granulomatous disease of unknown cause, most commonly affecting the lungs, which tends to afflict young adults in the prime of their lives. Recent data indicating that sarcoidosis mortality rates are rising in the U.S. (1) and Europe (2) highlight the inadequacy of current therapies. As noted in a recent NIH-sponsored sarcoidosis workshop, the lack of relevant animal, computer or in vitro models represents a bottleneck for progress towards understanding disease mechanisms and developing highly effective sarcoidosis treatments (3). The lack of useful disease models likely contributes to the current lack (zero) of investigator-initiated (RO1) projects supporting sarcoidosis research.
The long-term goal of this proposal is to develop a novel human sarcoidosis research model to fill the current void in the field, thereby expediting exploration of basic disease mechanisms and pre-clinical testing of novel therapies. The objective of this application, which is the first step towards achieving the long-term goal, is to develop a novel in vitro human granuloma model to represent abnormal granuloma formation in the context of sarcoidosis. In this regard, a growing body of evidence indicates that mycobacterial antigens are commonly harbored in sarcoidosis tissues, to which these patients are sensitized (4, 5). Our central hypothesis is that the pathological mechanisms of sarcoidosis can be modeled in vitro, as represented by abnormal granuloma formation in response to mycobacterial and other ubiquitous environmental antigens. The feasibility of our proposed model is supported by preliminary studies showing that subjects sensitized to Mycobacterium tuberculosis antigens (latent TB tuberculosis with a positive TB skin test) form well-organized granulomas readily in response to challenge with TB antigens, compared to healthy controls. This project is highly innovative and we feel has an excellent likelihood of leading to a critical breakthrough in the field of sarcoidosis research.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Observational study Blood draw only, observational study |
Other: No intervention, observational study only
No intervention. We are collecting blood for an ex vivo study
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Outcome Measures
Primary Outcome Measures
- Sarcoidosis patients, volunteers with latent TB, and healthy volunteer subjects will be recruited to donate peripheral blood for isolation of peripheral blood mononuclear cells. [2-4 years]
We hypothesize that patients with the active sarcoidosis phenotype will exhibit accelerated granuloma formation with higher IL-10(IL Interleukin)and IL-4 expression relative to patients with the self-limited sarcoidosis phenotype
Eligibility Criteria
Criteria
Inclusion Criteria:
- sarcoidosis, subjects (18 - 45 years of age), including 30 sarcoidosis, 15 latent TB and 15 healthy controls.
Exclusion Criteria:
- pregnant women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Biomedical Research Tower, 10th floor | Columbus | Ohio | United States | 43221 |
Sponsors and Collaborators
- Elliott Crouser MD
Investigators
- Principal Investigator: Elliott Crouser, MD, Ohio State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2012H0073