Glanzmann thrombasthenia (GT) is rare disorder of bleeding associated with defects in integrin αIIbβ3. Building upon our research in GT, Protheragen is remaining focused on advanced therapy development for improving the best management practices of GT. As your collaborator in GT drug development research, we offer comprehensive assistance to advance your research objectives.
Defective GP IIb/IIIa complex (integrin αIIbβ3) causes defective platelet aggregation in Glanzmann thrombasthenia (GT), a rare autosomal recessive bleeding disorder. GT was first described by Eduard Glanzmann in 1918 and manifests as mucocutaneous bleeding which includes epistaxis, menorrhagia, gingival hemorrhage, and prolonged post-operative and post-trauma bleeding. GT does not, however, spontaneously present with muscle or joint bleeds, unlike hemophilia.
Glanzmann thrombasthenia (GT) occurs due to inherited alterations in the ITGA2B and ITGB3 genes that code for the αIIb and β3 subunits of the platelet glycoprotein (GP) IIb/IIIa complex (integrin αIIbβ3). These mutations lead to an immanent inability to bind fibrinogen and von Willebrand factor (vWF) during the processes of blood clotting due to malfunction of this critical receptor on platelets.
Fig.1 In Glanzmann thrombasthenia (GT), αIIbβ3 deficiency results in loss of fibrinogen-mediated platelet bridging, leading to platelet dysfunction. (Gandhi P S, et al., 2024)
| Therapy | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Concizumab | Inhibits tissue factor pathway inhibitor (TFPI) to enhance thrombin generation and improve clot formation. | TFPI | NCT06234813 | Early Research |
| HMB-001 | Binds and stabilizes fibrinogen to promote platelet aggregation independent of GPIIb/IIIa. | Fibrinogen | NCT06211634 | Phase I/II |
| Coagulation Factor VIIa Variant | Bypasses the need for platelet aggregation by directly activating thrombin generation on platelet surfaces. | Tissue Factor (TF) | NCT04548791 | Phase I/II |
| Eptacog Alfa | Activates the extrinsic coagulation pathway independently of GPIIb/IIIa to promote fibrin clot formation. | Tissue Factor (TF) | NCT01876745 | Approved |
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.
Protheragen provides full-scope diagnostic and therapeutic development services aimed at improving the management of Glanzmann thrombasthenia (GT). Given the various molecular pathways that propel GT, we aim at developing innovative therapies with diverse and targeted approaches to address the significant unmet medical needs. Our group is specialized in designing precise disease models, which guarantees high fidelity assessment in the testing of safety, effectiveness, and therapeutic action of drugs.
β3 Knockout Model: Protheragen employs gene editing technology for creating a GT research transgenic mouse model by knocking out the β3 integrin (ITGB3) gene. These mice exhibit important phenotypes of GT such as increased bleeding time, dysfunction in platelet aggregation and clot retraction, with a normal level of platelets.
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
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