Autoimmune Diseases
Imbalanced iron metabolism is increasingly recognized as being involved in the pathogenesis and progression of autoimmune diseases. The complexity of this interaction between iron and the immune system reveals iron's function in the modulation of immune cell activity, inflammation, and oxidative stress. At Protheragen, we are committed to promoting the development of research on autoimmune diseases associated with iron metabolism. Our expertise is in the comprehension and management of iron metabolism abnormalities in autoimmune diseases, offering drug discovery and development solutions in this field.
Iron Metabolism Abnormalities in Autoimmune Diseases
Autoimmune diseases are inflammatory disorders where the immune system mistakenly targets the body's own healthy cells. This misfiring of immune activity weakens the capacity for normal immune regulation while amplifying unhelpful inflammatory responses, causing progressive damage to organs and surrounding tissues. Ferroptosis, by contrast, is a tightly regulated process of cellular demise driven by iron. Its signature features include an imbalance of intracellular iron, a collapse of the cell's antioxidant capacity, and peroxidation of lipids.
Fig.1 Ferroptosis's impact on various Immune cells. (Zheng, Y., et al., 2024)
Recent investigations have increasingly pointed to a likely connection between ferroptosis and the dynamics of autoimmune diseases, with immune cells positioned at the center of the interaction. Ferroptosis modulates immune cell behavior in several ways. When immune cells themselves undergo ferroptosis, their viability and function are compromised; this alteration in both cell numbers and activity subsequently modulates the immune response. On the other hand, the ferroptosis of non-immune cells produces DAMPs, followed by the immune response.
Classification of Iron Metabolism-related Autoimmune Diseases
The relationship between iron metabolism and autoimmune diseases is multifaceted and may differ depending on the nature of the condition. Recent research suggests that iron metabolism is associated with the onset and progression of the following autoimmune disorders.
Systemic Lupus Erythematosus (SLE)
SLE is an autoimmune disorder marked by excessive self-antibody production, persistent inflammation, and progressive damage to multiple organs. Individuals with lupus often exhibit defective iron transport and impaired iron incorporation into hemoglobin. Studies reveal that individuals with SLE have lower iron concentrations within and outside the bone marrow, as well as normal marrow cell proliferation.
Multiple Sclerosis
Multiple sclerosis is an inflammatory demyelinating autoimmune disease and a neurodegenerative disorder. Iron accumulation could be detected in the globus pallidus, caudate, and putamen, and in certain cortical areas of multiple sclerosis. The results of iron accumulation would result in ROS generation, ferroptosis induction, and inflammation enhancement, which might be significant in the pathogenesis of multiple sclerosis.
Rheumatoid Arthritis
Iron metabolism is associated with the development of rheumatoid arthritis, a chronic autoimmune inflammatory disease. Local iron overload has been documented within inflamed synovial tissue, prompting increased production of reactive oxygen species. This excess iron can damage synovial tissue, blood vessels, and the joints themselves, in part by promoting ferroptosis.
Other Autoimmune Diseases
Disturbance of iron metabolism is also involved in other autoimmune diseases such as myasthenia gravis, lupus nephritis, autoimmune hepatitis, Sjögren's syndrome, etc. Understanding the emerging complex dysregulation of iron homeostasis in autoimmune diseases would create new opportunities for the identification of novel diagnostic markers and for targeted therapeutic interventions.
Therapeutic Development for Autoimmune Diseases
| Diseases | Drug Name | Mechanism of Action | Targets | Research Phase |
| Systemic Lupus Erythematosus (SLE) | Deferiprone | Reduces renal tubular mitochondrial ROS and renal tubular inflammasome overactivity due to iron overload. | Iron overload | Preclinical |
| Ferrostatin-1 | Reduces iron-dependent lipid peroxidation in renal tubular cells. | GPX4, ACSL4 | Preclinical | |
| Rheumatoid Arthritis | Curcumin | Alleviate synovitis and cartilage deterioration by modulating iron-induced oxidative stress and inflammation in the joints. | Iron overload | Preclinical |
| N-acetylcysteine | Inhibit synovial inflammation due to iron-catalyzed ROS. | ROS, lipid peroxides | Phase II | |
| Multiple Sclerosis | Deferoxamine | Possibly reduces immune cell activation and degradation of acetylcholine receptors by curtailing excessive iron. | Iron overload | Phase I/II |
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
Leveraging our depth of expertise in the intricate relationship of iron metabolism and autoimmunity and integrated service platform, we offer an end-to-end solution that takes your project from concept to preclinical validation. We provide a one-stop, comprehensive solution for diagnostic, therapeutic, disease model development, and preclinical research, enabling researchers and scientists to better understand and study disease.
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 Autoimmune Diseases
It is no secret that strong and relevant animal models are essential in the successful progression of drug discovery and development, and our company provides many options and comprehensive services for animal model development and applications, designed to simulate the intricacies of iron metabolism-related autoimmune diseases.
| Diseases | Optional Models | Optional Species |
| Systemic Lupus Erythematosus (SLE) | Gpx4 knockout model, MRL-lpr model, NZB/w F1 model, etc. | Mice, Rats, Rabbits, Guinea Pigs, Canine Models, Non-human Primates, Other Species. |
| Rheumatoid Arthritis | Collagen type II induced model, Adjuvant induced model, Collagen antibody-induced arthritis, etc. | |
| Multiple Sclerosis | Experimental autoimmune encephalomyelitis (EAE) model, TMEV-induced demyelination model, Toxin-induced demyelination model, etc. | |
| Other Diseases | We also provide customized animal model development services for other autoimmune diseases related to iron metabolism. Please contact us for more details. |
Pharmacokinetics and Drug Safety Evaluation Services
Partner with Protheragen to unlock new therapeutic avenues in iron metabolism-related autoimmune diseases. Contact us today about how our end-to-end services can bring about real progression for your research.
References
- Zheng, Yingzi et al. "Targeting ferroptosis in autoimmune diseases: Mechanisms and therapeutic prospects." Autoimmunity reviews 23.11 (2024): 103640.
- Zeng, Liuting et al. "Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases." Cell death & disease 15.7 (2024): 481.