Blood Disorders
Blood disorders affect erythrocytes, leukocytes, platelets, and plasma, causing deficient transport and utmost impediment to oxygen and immunity, among other functions. It is now recognized that the disruption of iron homeostasis constitutes a fundamental factor in the causation and progression of a wide variety of hematological disorders. At Protheragen, we focus on iron metabolism while offering a comprehensive range of services to expedite the creation of novel diagnostics and therapeutics for blood disorders.
Overview of Blood Disorders
Hematological disorders encompass a range of conditions affecting the production and functioning of blood. Someone could be suffering from more well-known disorders, such as anemia, or more complex and life-threatening syndromes like myelodysplastic syndromes, leukemias, and lymphomas. Individuals could be facing a multitude of issues such as chronic fatigue, weakness, or even more complex and life-threatening conditions.
Fig.1 Maintaining iron balance throughout the body. (Cappellini, M. D., et al., 2022)
Iron Metabolism Abnormalities in Blood Disorders
The relationship between iron metabolism and blood disorders is complex and multi-layered. Deficiency of iron can result in some forms of anemia and is most typically seen in iron deficiency anemia (IDA), in which lack of iron limits hemoglobin formation and, therefore, delivery of oxygen. On the other hand, iron overload seen in disorders such as hereditary hemochromatosis or transfusional hemosiderosis (commonly seen in thalassemia or myelodysplastic syndromes) leads to the excess accumulation of iron in the body. The excess iron may produce reactive oxygen species, which generate oxidative stress and cell damage, resulting in the dysfunction of the liver, heart, pancreas, and some endocrine glands.
Fig.2 The role of iron mechanisms in the anemia of inflammation. (Marques, O., et al., 2023)
In addition, persistent inflammation, which occurs in several blood conditions, can disturb iron balance in the body. Inflammatory signals can elevate hepcidin, a key regulator of iron, leading to iron sequestration within macrophages and hepatocytes. This creates a "functional" iron deficiency, adding to the anemia of chronic disease. Grasping these multifaceted pathogenic mechanisms is essential for devising appropriate therapy strategies.
Therapeutic Development for Blood Disorders
| Categories | Description | Categories | Description | Categories |
| Iron-deficiency Anemia | Ferric maltol | Enables absorption of iron via a stable ferric iron-maltol complex, which bypasses limitations of the DMT1 transporter. | Duodenal iron absorption | Approved |
| Sickle-cell Anemia | Voxelotor | Stabilizes oxygenated HbS, reducing associated hemolytic damage while decreasing heme-related oxidative stress. | Hemoglobin S | Approved |
| Anemia of Inflammation | DISC-0974 | Inhibits the synthesis of hepcidin, which leads to an increase in iron release from macrophages via ferroportin. | Hemojuvelin (HJV) | Phase I/II |
| Congenital Dyserythropoietic Anemias | Zilurgisertib | The compound acts by selective ALK2 inhibition, reducing hepcidin synthesis and restoring normal iron homeostasis. | ALK2 (ACVR1) | 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
As a leading research service provider focused only on the disorders of iron metabolism, we offer a complete suite of services that aim to speed the translation of novel therapeutics into actionable therapies for a range of hematologic disorders. Our platform enables the development of diagnostic assays, advancement of therapeutic candidates, modeling of diseases, and preclinical evaluations and validation, thus empowering scientists and researchers globally to advance understanding and therapeutic intervention for these intricate diseases with accuracy and agility.
Therapeutic Development Services
Types of Iron Metabolism-related Blood Disorders
- Anemia of Chronic Disease
- Anemia of Inflammation
- Congenital Dyserythropoietic Anemias (CDAs)
- Iron-deficiency Anemia
- Sickle-cell Anemia
- Sideroblastic Anemias
- Thalassemia
- Atransferrinemia
- Myelodysplastic Syndromes
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
Animal Model Development Services for Blood Disorders
Researchers studying the blood disorders linked to iron metabolism require dependable animal models that closely mimic the disease processes in human individuals and can reliably predict the outcomes of therapeutic interventions. Our company specializes in designing and developing a wide variety of custom animal models spanning the entire spectrum of these disorders. In addition to developing the models, we offer characterization services that can be customized to meet the specific needs of a given study.
| Animal Models | Diseases | Types |
| LPS-induced model | Anemia of Inflammation | Chemical-induced model |
| IL-6 overexpression model | Anemia of Inflammation | Genetically engineered model |
| Complete Freund's adjuvant (CFA)-induced model | Anemia of Inflammation | Chemical-induced model |
| Cdan1 transgenic model | Congenital Dyserythropoietic Anemias | Genetically engineered model |
| Iron-deficient diet-induced model | Iron-deficiency Anemia | Diet-induced model |
| SAD-1 transgenic model | Sickle-cell Anemia | Genetically engineered model |
| Alas2 knockout model | Sideroblastic Anemias | Genetically engineered model |
| HbbTh3/+ mouse model | Thalassemia | Genetically engineered model |
| NHD13 transgenic model | Myelodysplastic Syndromes | Genetically engineered model |
| Benzene-induced model | Myelodysplastic Syndromes | Chemical-induced model |
Pharmacokinetics and Drug Safety Evaluation Services
Leveraging our customized services in animal models alongside cutting-edge drug development, Protheragen empowers researchers to advance the study and therapy of iron metabolism-related blood disorders, blending our deep understanding of iron metabolism. If you would like to see how our services can advance your work, do not hesitate to contact us.
References
- Marques, Oriana et al. "The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation." Blood 140.19 (2022): 2011-2023.
- Cappellini, Maria Domenica et al. "Iron metabolism and iron deficiency anemia in women." Fertility and Sterility 118.4 (2022): 607-614.