Interstitial Lung Disease (ILD)
EmphyCorp has been granted Orphan Drug
status by the FDA to develop N115 for the
treatment of Interstitial Lung Disease.
The intent of the Orphan Drug Act is to
stimulate the research, development, and
approval of products that treat rare
diseases. Since the Orphan Drug Act
passed, over 100 orphan drugs and
biological products have been brought to
market.
Interstitial Lung Disease (Diffuse),
includes a number of rare conditions
presenting with characteristic clusters of
clinical features, marked by an immune
response and containing an inflammatory
component. This disease classification
refers to a subset of approximately 130 to
2(X) rare pulmonary diseases that include
the fibrosing lung diseases and the
granulomatous diseases.
Interstitial lung diseases are
typically characterized by a marked
inflammation at the site of the lung
injury. This inflammatory process leads to
further destruction of surrounding healthy
lung tissue, and a continuation and
expansion of the sites of inflammation.
This inflammatory process results in the
production of reactive oxygen species,
including superoxide anions and hydrogen
peroxide, at the site of inflammation.
The functional changes reflect a restriction of airflow manifest by:
- Decreased vital capacity
- Decreased total lung capacity
- Decreased residual volume
- Decreased lung compliance
- Cyanosis (sign of severe hypoxemia; attributed to ventilation-perfusion mismatching)
- Late in the disease, one may see pulmonary hypertension due to destruction of the alveolar capillary bed
Nitric oxide is a known bronchodilator.
It has been used successfully in this
regard to treat patients with various
pulmonary diseases, including the
interstitial lung diseases. When
endogenous nitric oxide, is exposed to
oxygen radicals, it is converted to the
toxic oxidant nitrogen dioxide, and its
bronchodilating effect is mitigated.
Conversely, nitrogen dioxide is a known
deep lung irritant. It causes pulmonary
inflammation; lowers levels of lung
antioxidants; deteriorates respiratory
defense mechanisms leading to increased
susceptibility to respiratory pathogens
and increased incidence and severity of
respiratory infections; reduces lung
function, and worsens asthma and COPD
symptoms.
Reactive oxygen species, especially
superoxide anions, are known to compromise
lung function by increasing
bronchoconstrictions. As a result of the
increasing inflammation and the production
of reactive oxygen species, and the
decrease in nitric oxide that is believed
to occur with the interstitial lung
diseases, healthy tissue is damaged and
lung function is compromised.
Based on our present understanding of
the disease process involved with the
interstitial lung diseases, and supported
by the positive results obtained from the
bleomycin-induced pulmonary fibrosis rat
model study, it appears that an
intervention in the inflammatory process
that would result in a reduction in
reactive oxygen species and a subsequent
increase in nitric oxide could be an
effective way to intervene in the disease
process. This intervention would prevent
the further spread of inflammation and
lung damage caused by the production of
reactive oxygen species, such as
superoxide anions and hydrogen peroxide;
and increase lung function by increasing
bronchodilation.
Sodium pyruvate is a reactive oxygen
species (ROS) antagonist that has been
shown to neutralize oxygen radicals
(specifically lowering the overproduction
of superoxide anions), regulate the
production and level of other inflammatory
mediators, and regulate the synthesis of
nitric oxide. Sodium pyruvate also
increases cellular levels of glutathione,
a major cellular antioxidant, which is
reduced dramatically in antigen-induced
lung disease patients.
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