Sepsis

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to severe organ dysfunction and high mortality rates. As a leading Preclinical CRO, Alfa Cytology has dedicated significant efforts to exploring novel PARP inhibitor to combat this complex and challenging disease.

Introduction to PARP Inhibitor for Sepsis

Sepsis involves multiple dysregulated mechanisms in the host response. Poly (ADP-ribose) polymerase (PARP) is a key enzyme as its over-activation leads to cellular dysfunction and death. PARP inhibitors, such as olaparib, were originally developed for cancer treatment but have the potential to be repurposed for the treatment of non-oncological diseases such as sepsis. The pathophysiology of sepsis involves DNA damage, oxidative stress, and dysregulated inflammation, and studies have shown that PARP inhibitors are effective in protecting sepsis patients from hemodynamic dysfunction, metabolic dysfunction, and organ failure.

Fig. 1 Emerging role of PARP-1 in ischemic sepsis. (Ahmad A., et al. 2019)

PARP Inhibitor Development for Sepsis

The available preclinical evidence supports further investigation of repurposing clinically approved PARP inhibitors, like olaparib, as a novel therapeutic approach for the treatment of sepsis. The following clinically approved PARP inhibitors are used in sepsis models.

Experimental Model	Disease Modelled	PARP Inhibitor	Effects
Endotoxin-injected mice	Sepsis	Olaparib	Improved liver function and reduced inflammatory gene expression

Our Services

Through innovative research and advanced technology, Alfa Cytology delves into the mechanisms of PARP action and has the ability to help clients develop novel PARP inhibitors, as well as optimize the effectiveness of PARP inhibitors and identify their biomarkers, to accelerate the development of new therapies for sepsis.


Small Molecule Inhibitors Development	Peptide Inhibitor Development	Advanced Biomarker Identification	High-Throughput Screening (HTS)	Structure-Based Drug Design (SBDD)	Preclinical Modeling and Screening

Our Sepsis Modeling Services

Preclinical sepsis models play a crucial role in understanding the pathophysiology of the disease and assessing the efficacy of new therapeutic interventions. Several well-established animal models of sepsis have been developed and utilized in research. There are three types of animal models of sepsis: models of toxemia (e.g., LPS infusion), models of bacterial infection (e.g., models of venous, abdominal, or pulmonary infections), or models of host barrier disruption (e.g., models of cecum ligation and puncture, wounds).

At Alfa Cytology, we offer a range of sepsis models:

Peritoneal and Intravenous Sepsis Models
Pulmonary Sepsis Models
Cecal Ligation and Puncture

LPS-induced Sepsis Model
Fecal Peritonitis Model
Pathogen-Specific Models

Our Advantages

Efficient Therapeutic Screening - Our high-throughput screening capabilities and in vivo testing platforms accelerate the evaluation of novel drug candidates and combination therapies.

Integrated Data Analysis - At Alfa Cytology, our experienced team provides comprehensive data analysis and reporting to guide your research and development decisions.

Regulatory Compliance - We adhere to the highest standards of quality, safety, and ethical practices to ensure your preclinical studies meet regulatory requirements.

Alfa Cytology is committed to advancing the field of metabolic disease research and driving the development of novel PARP inhibitor. To achieve this goal, we actively engage in collaborative efforts with leading academic institutions and pharmaceutical companies. For more information about our PARP inhibitor development program for sepsis or to discuss potential collaborations, please don't hesitate to contact us.

Reference

Ahmad A., Vieira J. C., and et al. The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis. Pharmacol Res. 2019, 145: 104263.

For research use only. Not intended for any clinical use.