EVALUATING AGENTS FOR THE TREATMENT OF SEPSIS USING INFECTIOUS DISEASE MODELS

Sepsis is one of the 10 leading causes of death worldwide. According to the Centers for Disease Control, more than 1.5 million people in the United States contract sepsis yearly, and around 250,000 of these people die from its associated complications.

In 2015, sepsis added an additional $20.3 billion in healthcare costs alone in the US, and the incidence of sepsis and associated healthcare costs continues to increase. Despite many advances in care, fully effective treatment strategies for sepsis have unfortunately remained elusive.

Pathobiology of Sepsis

Sepsis is life-threatening organ dysfunction that develops as a result of dysregulated host response to uncontained microbial infection. The overall pathobiology of sepsis is complicated and involves early activation of both pro- and anti-inflammatory responses along with major modifications in nonimmunologic pathways.

How sepsis affects a patient is greatly influenced by their age and general health. Potential effective therapeutics for the prevention and treatment of sepsis include antimicrobial agents, vaccine strategies for causative organisms, mitigation of the dysregulated antimicrobial host response, and palliative care.

Infectious Disease Models of Sepsis

Antimicrobial and immunomodulatory agents have the potential to perform a number of actions that could prevent the establishment of sepsis and mitigate the complications of the resulting dysregulated host response.

Initial identification of effective antimicrobial agents generally starts at the in vitro stage, where candidate therapeutics are evaluated for their ability to inhibit the replication of or kill a range of clinically-relevant infectious agents. The in vitro characterization may also include identifying the prospective therapeutics’ mechanism of action and its ability to circumvent antimicrobial resistance.

Preclinical identification and testing of new therapeutics for the treatment of sepsis requires suitable animal models capable of characterizing microbial replication and the impact of the prospective therapeutic on the pathobiology of sepsis. The cascade of events leading to sepsis can be a direct effect of the systemic invasion of an infectious agent or its toxic product(s). Routes of systemic invasion include complications from peritonitis, bronchial infection and infected wounds, or direct exposure of the bloodstream to the infectious agent or its toxic products (endotoxemia), conditions that can be created in animal models of infection.

At Noble Life Sciences, we have established in vitro assays and animal models for the evaluation of bacterial sepsis. Animal models include murine peritonitis models using a single infectious organism (MRSA) or bacteremia from intestinal contents (cecal slurry). Our animal models for toxicology can be used to establish endotoxemia-induced sepsis.

These models can be performed with animals of various ages to mimic clinically relevant conditions and multiple end point analyses such as bacterial load, immunological biomarkers and histology, which can be utilized to evaluate the effectiveness and mechanism of the candidate therapeutic. The breadth of experience of Noble Life Sciences’ scientific and technical staff provides the ability to modify current models or develop custom infectious disease models to meet your goals in the development of therapeutics for the prevention and treatment of sepsis.

Multidisciplinary Approach to Preclinical Drug Development

Noble Life Sciences provides a broad range of preclinical drug discovery and development services. From in vitro analysis to animal models of infection and disease, toxicology, cell biology, molecular biology, immunology, and oncology, we can support your research and be a valuable addition to your scientific team. Our programs are designed to help you move your research from bench-to-bedside in an effective and timely manner.

Noble Life Sciences is one of Baltimore’s leading contract research organizations for preclinical studies. Our strategic location near Johns Hopkins gives us an advantage in supporting numerous biotechnology companies and universities in the area.

Contact us today to find out how we can help you achieve your preclinical goals.

2018-06-01T09:07:42+00:00May 22nd, 2018|Blog|