Acute Lung Inflammation (ALI) NHP Model

Acute Lung Inflammation (ALI) NHP Model

Discover Prisys Biotech’s cynomolgus monkey heart failure (EFrHF) model, designed to replicate human disease progression from AMI to chronic heart failure. Our clinically relevant NHP platform integrates advanced imaging, biomarker analysis, and pathology to accelerate cardiovascular drug development.
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Product Introduction

Prisys Biotechnologies provides a Non-Human Primate (NHP) model of Acute Lung Inflammation (ALI) for preclinical research. The model utilizes LPS-induced inflammation in cynomolgus monkeys to support the evaluation of pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of novel therapeutic candidates, particularly those intended for respiratory delivery.

 

 

Prisys Biotech's Acute Lung InflammationModel Features

 

  • Translational Species: Cynomolgus monkeys possess a respiratory system with anatomical and physiological similarities to humans, making them a suitable translational model for evaluating respiratory therapeutics.

  • Consistent Inflammation Induction: Our protocol for intratracheal LPS administration induces a consistent and transient inflammatory response, characterized by neutrophil influx and cytokine release, mirroring features of human ALI.

    • Multi-Modal Endpoint Analysis: We offer a suite of endpoints to characterize the local and systemic effects of test articles:

      • Computed Tomography (CT): Non-invasive imaging for longitudinal assessment of lung injury and inflammation.

      • BALF Analysis: Characterization of the lung environment through bronchoalveolar lavage fluid (BALF), including total and differential cell counts and biomarker quantification.

      • Systemic & Local Biomarkers: Measurement of pro-inflammatory cytokines (e.g., IL-6, TNF-α, IL-8, IL-1β) in both BALF and serum.

  • Concurrent PK/PD Assessment: The study design allows for the concurrent evaluation of pharmacokinetics and pharmacodynamics, enabling the analysis of exposure-response relationships.

  • Targeted Drug Delivery: We support drug delivery routes relevant to respiratory diseases, including intratracheal administration via spray.

 

 
 
 
 
 
 
 
 

 

Study design and clinical endpoints

Our study designs can be adapted to specific research objectives and generally follow a framework that captures the dynamics of inflammation and therapeutic intervention.

Study design:

 

Baseline Period: Acclimation of animals and collection of baseline BALF and serum samples. This period is also used for animal selection based on predefined criteria.

Dosing and PK Sampling: Administration of the test article. Blood samples for PK analysis are collected at multiple predefined time points following drug administration.

Inflammation Challenge: LPS is administered via inhalation to induce acute lung inflammation.

Post-Challenge Assessment: BALF and serum are collected at specified time points post-LPS challenge to evaluate the inflammatory response and the effects of the test article.

Longitudinal Monitoring: Throughout the study, animals are monitored for clinical observations and body weight.

 

 

Translational Endpoints for Drug Development:

 

Imaging: Longitudinal CT imaging to visualize and quantify lung opacities and consolidation.

BALF Analysis:

  • Total and differential cell counts (Neutrophils, Macrophages, etc.).
  • Pro-inflammatory cytokine levels (e.g., IL-6, IL-8, TNF-α).
  • Target engagement biomarkers.

Serum/Blood Analysis:

  • Pharmacokinetic (PK) profiling.
  • Systemic cytokine levels for PD assessment.
  • Complete Blood Count (CBC) and hematology.

Clinical Observations: Daily monitoring of animal health and activity.

 

 

Macro phages percentage in BAL fluid cells%
Macro phages percentage in BAL fluid cells%

key result and figure legend in LPS-Induced Acute Lung Inflammation Model

 

The NHP Acute Lung Inflammation ALI model exhibits pathological features relevant to the human condition, providing a system for testing therapeutic efficacy.

Longitudinal CT Imaging: CT scans show LPS-induced lung inflammation, visualized as ground-glass opacities in the left upper lobe and bilateral lower lobes. This endpoint allows for longitudinal tracking of injury and resolution.
Longitudinal CT Imaging: CT scans show LPS-induced lung inflammation, visualized as ground-glass opacities in the left upper lobe and bilateral lower lobes. This endpoint allows for longitudinal tracking of injury and resolution.
 
Inflammatory Cell Infiltration in BALF: Following LPS challenge, an inflammatory cascade is observed in BAL fluid, indicated by an increase in neutrophil percentage and a corresponding decrease in the macrophage population.
Inflammatory Cell Infiltration in BALF: Following LPS challenge, an inflammatory cascade is observed in BAL fluid, indicated by an increase in neutrophil percentage and a corresponding decrease in the macrophage population.

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The LPS-Induced Acute Lung Inflammation Model elicits a pro-inflammatory cytokine response. An elevation of IL-6 is detected in both BALF (local) and serum (systemic), confirming a quantifiable inflammatory response that can be modulated by test articles.

Let Prisys Biotech be your partner in accelerating the discovery and development of innovative Acute Lung Inflammation treatments.

 

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