Sideroblastic Anemias
Sideroblastic anemia is an uncommon form of anemia due to abnormal utilization of iron in erythropoiesis. There are various forms of sideroblastic anemia, all of which are characterized by the presence of ringed sideroblasts in the bone marrow. As the leading research service provider specializing in the field of iron metabolism disorders for drug discovery and development, Protheragen has integrated cellular, proteomic, and biochemical technologies to provide customers with a comprehensive range of services to support their drug research and development for sideroblastic anemias.
Overview of Sideroblastic Anemias
Sideroblastic anemia is caused by defective erythropoiesis in heme synthesis. Like many other anemias, sideroblastic anemias may be either hereditary or acquired. Because of the lack of exact numbers concerning incidence and prevalence, researchers do not have reliable information about the epidemiology of the disorder. The disease spans a wide age range, from infants and those with congenital forms to middle-aged and older people.
- Hereditary Sideroblastic Anemias
Hereditary sideroblastic anemias result from mutations in genes located on the X chromosome, such as ALAS2, ABCB7, and GRLX5, as well as genes located on autosomal chromosomes and mitochondrial genes.
- Acquired Sideroblastic Anemias
Acquired forms of sideroblastic anemias are classified as primary, with RARS serving as a subtype of the myelodysplastic syndrome, or secondary, resulting from certain drugs, toxins, a lack of copper, or a chronic neoplastic disease.
Fig.1 The histomorphology of bone marrow and peripheral blood in sideroblastic anemia. (Abu-Zeinah, G., and DeSancho, M. T., 2020)
Iron Metabolism Abnormalities in Sideroblastic Anemias
Sideroblastic anemias refer to a class of heterogeneous blood disorders that share a common feature: the existence of ring sideroblasts in the bone marrow. These abnormal precursors of red blood cells are characterized by an excessive buildup of non-heme iron in the mitochondria, which forms a ring around the nucleus. This iron buildup stems from a basic disruption of the pathways of iron and heme metabolism, which results in ineffective erythropoiesis and anemia.
Fig.2 Sideroblastic anemia subtypes involve specific cell and mitochondrial heme pathway defects. (Abu-Zeinah, G., and DeSancho, M. T., 2020)
Therapeutics Development for Sideroblastic Anemias
Therapy targets for sideroblastic anemias concentrate on reducing ineffective erythropoiesis, enhancing hemoglobin production, controlling iron overload, and, more recently, correcting certain genetic abnormalities.
| Drug Name | Mechanism of Action | Targets | Research Phase |
| Pyridoxine | Cofactor for the ALAS2 enzyme and enhances heme synthesis. | Bile acid receptor FXR | Approved |
| Deferoxamine | Organ protection by iron removal and chelation. | Iron overload | Approved |
| Luspatercept | Inhibits SMAD2 and SMAD3 signaling by binding TGF-β superfamily ligand. | ACVR2B | Approved |
| Imetelstat | A telomerase inhibitor. | Telomerase | Phase III |
| Lentiviral vector (ALAS2) | To target ALAS2 expression in erythroid cells. | ALAS2 | 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
As a research service provider that focuses on iron metabolism and hematologic diseases, we provide the entire range of services to develop diagnostic, therapeutic, and disease models relevant to the research, development, and application of drugs for sideroblastic anemias.
Therapeutic Development Services
- Small Molecule Drug Development
- Cell Therapy Development
- Gene Therapy Development
- Therapeutic Protein Development
Animal Model Development Services for Sideroblastic Anemias
Animal models are of great value when studying the genetic, molecular, and metabolic bases of sideroblastic anemias, as they allow analysis of the pathophysiology of the human condition, the testing of therapeutic approaches, and drug efficacy in a controlled environment. We focus on working with you to provide customized animal model development services that empower your sideroblastic anemias research. We offer a one-stop solution, covering early-stage model development to model validations, phenotypic characterizations to the subsequent research to advance your findings.
Genetically Engineered Models
Genetically engineered animal models replicate hereditary sideroblastic anemia by introducing specific genetic defects in heme biosynthesis pathways.
- Alas2 knockout model
- Slc25a38 deficient model
- GLRX5 deficient model
- And more
Pharmacokinetics and Drug Safety Evaluation Services
Apart from customized animal models for sideroblastic anemias, Protheragen's services also include an integrated preclinical package, which consists of pharmacokinetic studies and drug safety evaluation, significantly accelerating therapeutic development. Collaborate with us and achieve the best for your sideroblastic anemia drug discovery programs. Contact us today to talk about your project and how our comprehensive services can assist you.
Reference
- Abu-Zeinah, Ghaith, and Maria T DeSancho. "Understanding Sideroblastic Anemia: An Overview of Genetics, Epidemiology, Pathophysiology and Current Therapeutic Options." Journal of blood medicine 11 (2020): 305-318.