Hereditary Hemorrhagic Telangiectasia (HHT)
The autosomal dominant trait hereditary hemorrhagic telangiectasia (HHT) results in multi-organ dysplastic lesions of the vasculature that can trigger several physiologic cascades towards a diverse spectrum of cardiovascular diseases. Dedicated to promoting rare cardiovascular diseases such as HHT therapy discovery, Protheragen provides a complete preclinical solution for drug discovery and development.
Introduction to Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder, with a frequency of about 1 in 5000, characterized by the presence of vascular malformations (VMs). These lead to chronic bleeding, acute hemorrhage, and shunting‐related complications through VMs. Up to 78% of HHT individuals develop hepatic arteriovenous malformations resulting in a hyperdynamic circulatory state due to hepatic/portal shunting. This can lead to high-output cardiac failure if the tissue is not adequately perfused despite increased cardiac output.
Fig.1 Target of therapy in HHT disease. (Al Tabosh, T., et al., 2024)Pathogenesis of Hereditary Hemorrhagic Telangiectasia (HHT)
HHT, also known as Osler-Weber-Rendu syndrome, is an autosomal dominant inherited systemic fibrovascular dysplasia.
It is often related to mutations in the endoglin (ENG) and activin A receptor-like type 1 (ACVRL1/ALK1) genes. It results from loss-of-function (LOF) mutations of some elements of the mostly endothelial BMP9-10/ENG/ALK1/SMAD4 signaling cascade, which plays a pivotal role in the maintenance of vascular quiescence.
Fig.2 Diagnostics of HHT. (Hammill, A. M., et al., 2021)Therapeutics Development for Hereditary Hemorrhagic Telangiectasia (HHT)
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Bevacizumab | Blockage of vascular endothelial growth factor (VEGF), to reduce abnormal blood vessel growth that can cause the bleeding of the disease. | VEGF-A | NCT06039124 | N/A |
| VAD044 | Oral allosteric AKT1/2 inhibitor that modulates the TGF-β signaling pathway, decreasing bleeding episodes and inducing vascular remodeling. | Akt | NCT05406362 | Phase II |
| Tacrolimus | Restores normal endothelial cell function, prevents abnormal blood vessel formation, and reduces bleeding episodes associated with the disease. | FKBP | NCT04646356 | Phase II |
| Pomalidomide | Exhibiting antiangiogenic and immunomodulatory effects, suppressing the formation of abnormal blood vessels. | CRBN, IKZF | NCT03910244 | Phase II |
| Nintedanib | Blocking several tyrosine kinases that promote the growth of blood vessels, and decreasing the development of abnormal blood vessels. | RTKs | NCT04976036 | Phase 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
Through this end-to-end offering of diagnostics, therapeutics, and disease model production, we enable our partners to expedite research and deliver better therapeutics to individuals. With the latest, cutting-edge technology and years of experience with us, we provide a variety of preclinical services from pharmacokinetic studies to drug safety studies. Through the use of sophisticated disease models and the latest analysis techniques, we deliver accurate and dependable results up to industry standards.
Therapeutic Development Services
Animal Model Development for HHT
Animal models are critical tools for dissecting the multifactorial pathophysiology of HHT, discovering therapeutic targets, and testing potential drugs for efficacy and safety in a controlled setting. Tailor-made animal model development services amid an increasing understanding of the need for accurate and predictive models, our company has maintained a dedication to leveraging new technologies and techniques to provide unique, custom services for every project that translates research from the bench to the bedside quicker.
Genetically Engineering Animal Model
Animal models for HHT involve genetically engineering animals to carry specific mutations associated with the disease, causing symptoms similar to the disease.
- Eng+/– model
- Alk1+/– model
- Alk1-iKO model
- BMP9/10 immune blockade model
- Other models
Committed to the success of our clients, Protheragen is focused on addressing the special challenges in rare cardiovascular diseases. By offering customized solutions and a relentless dedication to excellence, we earn the opportunity to be a reliable collaborator in the trek from concept to application. If you wish to avail our services, feel free to get in touch with us.
References
- Al Tabosh, Tala et al. "Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances." The Journal of clinical investigation 134.4 (2024): e176379.
- Hammill, Adrienne M et al. "Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management." Hematology. American Society of Hematology. Education Program 2021.1 (2021): 469-477.
For research use only, not for clinical use.