Asthma, a chronic inflammatory disease of the airways, manifests through symptoms such as coughing, shortness of breath, and respiratory obstruction, which can be life-threatening in severe cases. The majority of asthma patients suffer from allergic asthma, closely linked to the Th2 signaling pathway-mediated airway inflammatory response. This has led to the development and commercialization of several antibody drugs targeting key points in the Th2 pathway, such as omalizumab (IgE antibody), mepolizumab (IL-5 antibody), dupilumab (blocks IL-4 and IL-13 signaling), and tezepelumab (TSLP antibody).
NHP Asthma Models at Prisys Biotech
Prisys Biotech has successfully established sophisticated cynomolgus monkey (NHP) models of allergic asthma. Leveraging these models, our scientific and technical teams have significantly advanced the preclinical efficacy evaluation of various new drugs, including small molecules, antibodies, and small nucleic acid drugs. Our extensive experience in evaluating key targets within the Th2 signaling pathway, such as TSLP, IL-4, IL-5, IL-13, IgE, and ST2, positions us as leaders in this field.
Key Features of Prisys Biotech's NHP Asthma Models
Comprehensive Respiratory Function Testing
Respiratory dysfunction is a critical indicator in asthma models. At Prisys Biotech, we employ internationally recognized gold-standard equipment and protocols (e.g., Aerogen vibrating mesh nebulizers) in large animal bronchial challenge tests, ensuring high-precision aerosol induction and accurate respiratory function assessment.
Allergen Exposure and Sensitization Protocols
OVA Induced Asthma:
Allergen: Ovalbumin
Sensitization: Intraperitoneal (IP) injection
Booster/Challenge: Intratracheal (IT) inhalation
HDM Induced Asthma:
Allergen: House Dust Mite (HDM)
Sensitization: IP injection or IT inhalation
Booster/Challenge: IT inhalation
Primary endpoints for these asthma models include:
- Lung Inflammation: Pro-inflammatory cytokines and bronchoalveolar lavage fluid (BALF) analysis
- Lung Biopsy and Clinical Pathology: H&E/PAS staining, immunohistochemistry (IHC)
- Pulmonary Function Tests: Forced vital capacity (FVC), compliance, airway response (PC50)
- Hematological and Serological Tests: Complete blood count (CBC) and enzyme-linked immunosorbent assay (ELISA)
Pathophysiology and Characteristics of NHP Asthma Models
The pathogenesis of allergic asthma in cynomolgus monkeys is closely related to the Th2 signaling pathway. Upon allergen sensitization and challenge, levels of Th2 pathway-related cytokines significantly increase, presenting typical asthma pathology such as elevated airway resistance, decreased dynamic lung compliance, increased eosinophil and IgE levels, and lung inflammatory cell infiltration. Interventions with positive reference drugs can improve multiple asthma symptoms in these models simultaneously.
Conclusion
Despite the lack of extensive reports and establishment of asthma models in NHPs for drug efficacy and pharmacological assessment, Prisys Biotech has made significant strides in this area. Our comprehensive protocols, combining literature results with our expertise in NHP pulmonary diseases, ensure high repeatability and consistency. We have established the necessary major endpoints for this asthma model, particularly for cynomolgus monkeys, including clinical bronchoscopy, lung biopsy, and pulmonary function testing.
In summary, Prisys Biotech's innovative NHP asthma models are instrumental in driving preclinical drug efficacy studies, contributing to the development of new therapeutic strategies for asthma.
By utilizing these advanced models, Prisys Biotech continues to lead the field in preclinical asthma research, supporting the development of novel therapies aimed at improving patient outcomes.
Key words: NHP asthma model, Prisys Biotech, preclinical drug studies, allergic asthma, Th2 signaling pathway, respiratory function testing, OVA induced asthma, HDM induced asthma, pulmonary function tests
