Rare and Orphan Lung Diseases
Rare and orphan lung diseases are those that affect fewer than one in 2,000 people and up to 80% of these diseases are caused by genetic factors. There are over 6,000 such disorders, many of which are also Orphan diseases; those diseases that may be of limited interest to medical or scientific communities, with limited treatment and/or ongoing development.
As many rare diseases are heavily influenced by genetic background, the development of animal models which recapitulate the disease phenotype can be a major development hurdle for the study of rare diseases.
RELEVANT, TRANSLATIONAL, AND REPRODUCIBLE OUTCOMES
Measuring lung physiology of novel models to properly characterize phenotypes of rare and orphan lung diseases is vital during new strain development. As these differences may appear transiently or with easily missed hallmarks, it is imperative to use an extremely sensitive system to quantify the data.
The flexiVent facilitates highly sensitive and reproducible phenotype characterization to delineate the difference between even minor differences in disease presentation with very small subject groups. Detailed respiratory mechanics measurements and the option to configure experimental conditions allows researchers to reduce the time required for development and subsequent studies using novel strains, saving both time and resources.
- Cox, Andrew, et al. “Simultaneous disruption of five serpinA1 genes in mice using CRISPR/Cas9 to generate the first animal model of alpha-1 antitrypsin deficiency.” Mol Ther 23 (2015).
- Hsieh, Wan-Yu, et al. “Single-walled carbon nanotubes induce airway hyperreactivity and parenchymal injury in mice.” American journal of respiratory cell and molecular biology 46.2 (2012): 257-267.
- Sunil, Vasanthi R., et al. “World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung.” Experimental and molecular pathology 102.1 (2017): 50-58.
REPEATED VENTILATORY PARAMETERS.
The ability to repeatedly follow conscious subjects provides valuable insight into the overall lung function of a subject with minimal user intervention and invasiveness. Plethysmography is used to highlight ventilatory parameter changes such as breathing frequency, tidal volume, peak inspiratory or expiratory flows and is especially valuable in interventions requiring consciousness such as smells, aerosols or other stimuli. It offers a powerful means of rapidly screening subjects based on changes in subject metrics. The longer time periods available in these studies work especially well for longitudinal studies and where a disease phenotype results in very fragile subjects that can not handle more invasive measures.
- Povedano, Juan Manuel, et al. “Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.” eLife 7 (2018): e31299.
- Hurst, Brett L., et al. “Evaluation of antiviral therapies in respiratory and neurological disease models of Enterovirus D68 infection in mice.” Virology 526 (2019): 146-154.