New Minipig Model for Stress-Free Monitoring of Drug Effects on Cortisol

Scantox, in partnership with Lundbeck, has developed a unique stress-free blood sampling method for minipigs. This innovative minipig model allows a deeper understanding of how drugs affect the circadian cortisol profile. Cortisol is produced by the adrenal glands, and its activation is a key indicator of stress. It is part of the hypothalamic-pituitary-adrenal (HPA) axis.

Traditional sampling methods often introduce stress, leading to biased and inconsistent results. Accurate measurements are crucial to understanding how drugs influence stress response and maintain homeostasis. Our stress-free blood sampling method offers significant benefits for pharmaceutical companies, as outlined below.

Minipig Model Development

At Scantox, we rely on Göttingen minipigs for various study types, including PK/PD safety pharmacology, and general toxicology studies. Minipigs are particularly relevant as model systems due to their physiological and anatomical similarities to humans.

To minimize animal stress, we have developed a method that employs surgically implanted catheters and sampling via connected tubings, facilitating frequent blood sampling without direct contact and without causing pain or disturbance to the minipigs. The approach is critical to ensure the animals remain calm and undisturbed while blood samples are collected, for instance, every 20 minutes over 24 hours. Our highly trained animal technicians acclimate the animals for 3-4 weeks before the first sampling. This approach familiarizes them with the laboratory environment and research staff, fostering a high sense of comfort in staff and procedures. The method guarantees the reliability of physiological data and meets the highest animal welfare standards.

Key Findings

This technical solution has led to several critical insights outlined below:

1. Validation of stress-free sampling: The model confirms that we can take reliable and consistent physiological measurements under completely stress-free conditions that capture the natural cortisol fluctuations during the day. These measurements align with observations made in humans.
2. Validated effects of tested drugs on cortisol levels:  The CRH receptor antagonist, Verucerfont, lowered cortisol levels without disrupting natural rhythms. The serotonin-norepinephrine reuptake inhibitor, Venlafaxine, elevated cortisol levels and disrupted the cortisol rhythms. These results support prior research in the field observed in other model systems.

Benefits for Pharmaceutical Companies

The study’s findings offer substantial benefits to the pharmaceutical industry:

• 24-hour cortisol monitoring: Testing cortisol levels around the clock provides comprehensive diurnal and ultradian rhythms data. This continuous monitoring helps understand the full impact of drug administration on cortisol dynamics.
• Correct dose at the right time: The minipig model provides insights for determining the best timing for drug administration and minimizing disruptions to physiological rhythms. For example, using this model in early development phases can refine therapeutic dosing strategies, enhancing the outcomes of clinical trials.
• Animal welfare & quality data: Maintaining high animal welfare standards aligns with ethical research practices and ensures high-quality data collection.
• Regulatory support: The data from this model can aid in regulatory submissions, demonstrating the drug’s impact and safety.

Relevance for Neurological and Stress Disorders

The stress-free blood sampling method for minipigs represents a sensitive and promising approach for characterizing drug effects on cortisol levels. It exemplifies Scantox’s thought leadership in applying minipigs and neurology disease-related research. The model is highly relevant for the development of more effective treatments for neurodegenerative diseases and stress-related conditions such as depression and anxiety.

Scantox combines rigorous scientific methodology with a clear commitment to ethical standards and data integrity, offering a more accurate approach to drug development. With decades of experience, we can manage everything from in vivo efficacy models to regulatory toxicology, drug formulation, and bioanalysis. These comprehensive capabilities and timely communication ensure seamless integration and reliable results and reports at every research stage.

We invite you to contact our scientific experts to learn how they can assist your drug development efforts!