Due to its uncommon occurrence and complexity, thrombocytopenia absent radii (TAR) syndrome remains an unmet therapeutic medical need. Protheragen is poised to offer customized services and complete assistance by leveraging our wide-ranging knowledge in TAR syndrome therapy development to aid your transition from TAR syndrome therapy research to commercialization.
Thrombocytopenia absent radii (TAR) syndrome is rare congenital disorder which has two distinguishing features: thrombocytopenia or low blood platelet count and absence or underdevelopment of the radius bone in the forearm. This syndrome usually manifests itself in infancy or early childhood and the severity often differs in the individual affected. The condition of thrombocytopenia increases the risk for bleeding tendencies in the individuals with TAR syndrome while limb deformities and functional limitations can arise from the lack of radius bone.
Fig. 1 Inherited thrombocytopenia pathogenic genes related to megakaryopoiesis, platelet formation, etc. (Almazni, Ibrahim, et al., 2019)
The pathogenesis of thrombocytopenia absent radii (TAR) syndrome is believed to be multifactorial, involving genetic and developmental factors. TAR syndrome is primarily associated with mutations in the RBM8A gene on chromosome 1q21.1. This gene encodes a protein involved in the processing of messenger RNA. Mutations in RBM8A disrupt normal megakaryocyte development in the bone marrow, leading to reduced platelet production and thrombocytopenia.
Thrombocytopenia
RBM8A deficiency impairs megakaryocyte maturation, leading to defective proplatelet formation and bone marrow megakaryocyte malformations with severe neonatal thrombocytopenia that usually improves with age.
Radial Aplasia
Radial dysplasia is caused by disruption of mRNA processing of RBM8A-dependent skeletal development genes such as TBX5, resulting in bilateral absence of the radii but preservation of the thumbs, a key distinction from other radial defects.
Currently, therapeutic strategies for thrombocytopenia absent radii (TAR) syndrome focus primarily on symptom relief and supportive care, such as platelet transfusions for thrombocytopenia and orthopedic interventions for limb abnormalities. However, these approaches do not target the underlying genetic abnormalities that cause the condition. Developing targeted therapies for the genetic defects that underlie TAR syndrome is critical to addressing the complex medical needs.
| Therapy | Types | Targets | Mechanism of Action | Development Stage |
|---|---|---|---|---|
| Eltrombopag | Small molecule | Thrombopoietin receptor (TPOR) | Stimulates megakaryocyte proliferation and differentiation | Approved |
| Romiplostim | Peptide agonist | TPOR | Mimics TPO to boost platelet production | Approved |
| AAV Gene Therapy | Gene Therapy | RBM8A gene | Delivers functional RBM8A to hematopoietic stem cells | Preclinical |
| Splicing Modulators | Small molecule | Exon junction complex (EJC) | Rescues aberrant mRNA processing in RBM8A-deficient cells | Discovery phase |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
At Protheragen, our unwavering commitment lies in delivering state-of-the-art diagnostic and therapeutic development services tailored specifically for thrombocytopenia absent radii (TAR) syndrome. Our expertise is centered around the development of innovative therapies spanning multiple molecular classes, meticulously studied in intricately crafted disease models during the preclinical phase.
Genetically engineered model facilitates targeted treatment development by reproducing thrombocytopenia and bone defects in TAR syndrome.
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for thrombocytopenia absent radii (TAR) syndrome through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
Myeloproliferative Disorders (MPDs)
Bone Marrow Failure Syndromes (BMFS)
