Development of a Novel Human In Vitro Sarcoidosis Model
| Status: | Completed |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/2/2016 |
| Start Date: | April 2012 |
| End Date: | April 2015 |
| Contact: | Elliot Crouser, MD |
| Email: | elliot.crouser@osumc.edu |
| Phone: | 6147-293-4975 |
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.
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.
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.
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.
Inclusion Criteria:
- sarcoidosis, subjects (18 - 45 years of age), including 30 sarcoidosis, 15 latent TB
and 15 healthy controls.
Exclusion Criteria:
- pregnant women
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