Inflammatory Bowel Disease (IBD)
In individuals with inflammatory bowel disease (IBD), systemic iron-deficiency anemia develops due to chronic inflammation stimulating the hepatic secretion of hepcidin, liver iron hormone, while locally within the intestine, there is iron overload and associated oxidative stress that induces ferroptosis. Protheragen is actively providing research services on IBD, particularly its association with iron metabolism, to advance research and therapy development. We offer complete and integrated services to assist researchers and scientists in meeting their novel and creative targets.
Overview of Inflammatory Bowel Disease (IBD)
Crohn's disease and ulcerative colitis fall under the umbrella of IBD, which is associated with persistent and chronic inflammation of the gastrointestinal tract. It has been linked with many symptoms and complications, the most notable of which is chronic iron deficiency anemia (IDA).
IDA is among the most prevalent and notable extra-intestinal symptoms of IBD. More than half the people diagnosed with IBD suffer from it. Iron deficiency anemia also leads to reduced quality of life and an increase in morbidity and potentially even higher mortality. Iron deficiency is the consequence of consistent inadequate intake, malabsorption, which could include duodenal involvement or surgical removal, and chronic blood loss resulting from ulcerative mucosal inflammation.
Fig.1 IBD inflammation is mostly hepcidin-driven. (Mahadea, D., et al., 2021)
Furthermore, the infiltrating immune cells during the inflammatory process consume oxygen from the affected epithelial tissue region, resulting in local hypoxia. HIF activation augments iron absorption by modulating the messenger RNA of pathways involved in duodenal iron transport. Due to the blockade of iron efflux by hepcidin-mediated FPN degradation, iron accumulates in enterocytes, which leads to ferroptosis.
Iron Metabolism Abnormalities in Inflammatory Bowel Disease (IBD)
Ferroptosis is a distinct type of non-apoptotic cell death that is iron-dependent and involves lipoperoxidation; it has been linked to the pathogenesis of IBD. As a defining feature of some intestinal disorders like IBD, there is an abnormal increase in the intestinal epithelial cell death that results in significant epithelial erosion. In IBD, the chronic inflammation is maintained by ferroptosis through the overabundant generation of reactive oxygen species (ROS), iron, and unchecked lipid peroxidation, resulting in the death of intestinal epithelial cells and erosion of the epithelium.
Fig.2 Ferroptosis's role in IBD. (Ocansey, D. K. W., et al., 2023)
Therapeutics Development for Inflammatory Bowel Disease (IBD)
| Drug Name | Mechanism of Action | Targets | Research Phase |
| Ferric Carboxymaltose | Intravenous iron bypasses enteral absorption, raising hemoglobin with less oxidative stress. | Systemic iron replenishment | Approved |
| Ferrostatin-1 | It blocks lipid ROS accumulation and ferroptosis by scavenging alkoxyl radicals, protecting intestinal epithelial cells. | Lipid peroxidation/GPX4 | Preclinical |
| Fucoidan | It inhibits MSR1-based ferritin-loaded EV uptake, reducing macrophage activation and colonic inflammation. | MSR1 | Preclinical |
| Deferiprone | It chelates labile iron, inhibiting Fenton reactions, which decreases lipid peroxidation and colitis severity. | Intracellular iron chelation | Phase II |
| hucMSC-Ex | It inhibits lipid peroxidation and ferroptosis by targeting ACSL4 via miR-129-5p, reducing intestinal inflammation and restoring damage. | ACSL4 | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
Protheragen harnesses expertise in iron metabolism and IBD to offer integrated drug development services, which include everything from discovery to preclinical validation. We specialize in biomarker development and validation, and design and develop diagnostics, therapeutics, and disease models. We also offer pharmacokinetics and drug safety assessments of your drug candidates before commercialization, providing preclinical services in a comprehensive manner.
Therapeutic Development Services
- Small Molecule Drug Development
- Cell Therapy Development
- Gene Therapy Development
- Therapeutic Antibody Development
- Therapeutic Peptide Development
- Therapeutic Protein Development
Animal Model Development Services for IBD
To understand disease progression and evaluate the effectiveness and safety of new therapeutics, studying animal models is essential. Through our animal model development services, we equip investigators with dependable platforms for the discovery and development of therapies for IBD. We have a broad collection of established and custom-developed animal models that mirror various aspects of human IBD for sophisticated and comprehensive study.
| Genetically Engineered Model | |
| Animal models are created for research through genetic alteration, and spontaneous and heritable forms of IBD are developed. | |
| Optional models | IL-10 knockout model, HLA-B27 transgenic model, etc. |
| Chemical-induced Model | |
| Chemically induced models of IBD are created through the administration of specific chemicals aimed at causing inflammation of the gastrointestinal tract. | |
| Optional models | TNBS-induced model, DSS-induced model, Oxazolone-induced model, etc. |
| Adoptive Transfer Model | |
| The model of IBD is created through the transfer of CD45RBhighCD4+ T cells into immunodeficient mice. | |
| Optional models | CD4+ T-cell transfer model, etc. |
Pharmacokinetics and Drug Safety Evaluation Services
Partner with Protheragen today to expedite your IBD research and develop novel therapies that focus on the synergy of inflammation with iron dysregulation. Contact us to discover how deep expertise coupled with our comprehensive services can enhance your scientific research initiatives.
References
- Mahadea, Dagmara et al. "Iron Deficiency Anemia in Inflammatory Bowel Diseases-A Narrative Review." Nutrients 13.11 (2021): 4008.
- Ocansey, Dickson Kofi Wiredu et al. "Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review)." International journal of molecular medicine 51.6 (2023): 53.