Loeys-Dietz Syndrome
Loeys-Dietz syndrome is an autosomal dominant genetic disorder with severe and sometimes life-threatening vascular involvement. A leader in therapy innovation, Protheragen offers one-stop drug discovery and development services for rare cardiovascular diseases such as Loeys-Dietz syndrome. Focused on diagnostics, therapeutics, and disease model development, we are committed to driving innovation in these vital areas.
Introduction to Loeys-Dietz Syndrome
Loeys-Dietz syndrome is a vascular disorder (aneurysms and/or dissection) syndrome with skeletal, craniofacial, and cutaneous findings. The specific incidence of Loeys-Dietz syndrome is uncertain although thought to be in the order of 1:50,000. The principal causes of morbidity and premature death in Loeys-Dietz syndrome are aortic dilatation at the level of sinuses of Valsalva, susceptibility to aortic dissection and rupture, mitral valve prolapse (MVP) with or without regurgitation, and enlargement of the proximal pulmonary artery.
Fig.1 SMAD2, SMAD3, TGFB2, and TGFB3 mutation frequency to date. (Schepers, D., et al., 2018)Pathogenesis of Loeys-Dietz Syndrome
Loeys-Dietz syndrome is a rare autosomal-dominant connective tissue disease involving genetic mutations in the transforming growth factor-β (TGF-β) signaling pathway. Immunohistochemistry revealed enhanced expression of TGF-β receptors TGFBR2 and TGFBR3, as well as intracellular TGF-β effectors SMAD2 and SMAD3, in the media of the aorta of individuals with Loeys-Dietz syndrome, indicating that the TGF-β pathway is important in Loeys-Dietz syndrome aortic aneurysm and dissection formation.
Fig.2 Aortic and arterial aneurysms in individuals with Loeys-Dietz syndrome. (Lynch, C. P., et al., 2021)Therapeutics Development for Loeys-Dietz Syndrome
| Drug Name | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| Losartan | This leads to reduced TGF-beta signaling and slows the progression of aortic aneurysm formation by inhibiting the angiotensin II receptors. | AT1R | Phase II |
| Atenolol | Lowering the heart rate and blood pressure using selective beta-1 blockade and decreasing hemodynamic stress on the aortic wall. | β1-adrenergic receptor | Phase II |
| Dexamethasone | Reverses abnormal elastin production and collagen 1 secretion in Loeys-Dietz syndrome fibroblasts. | GR | 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
With innovative technology and expertise, we provide efficient, reliable solutions for specific challenges associated with rare cardiovascular diseases. Through our comprehensive range of customized services, we support the entire therapeutic product lifecycle, from early concept to application, and enable our clients to reach their instrumental milestones, with our diagnostics, therapeutics, and disease model development services. We provide comprehensive preclinical services with a one-stop shop that allows you to combine pharmacokinetic studies and drug safety tests, ensuring a robust chain of drug development services.
Therapeutic Development Services
Animal Model Development for Loeys-Dietz Syndrome
The construction of animal models for Loeys-Dietz syndrome has been necessary to elucidate the basis of this rare cardiovascular disease and to test potential therapeutics. Our company provides customized animal model development services for Loeys-Dietz syndrome, allowing scientists to expedite discoveries for diagnosis and therapy.
Genetically Engineered Animal Models
Generation of genetically engineered animal models for Loeys-Dietz syndrome entails the insertion of specific mutations into genes, such as TGFBR1 or TGFBR2, to mimic the disease phenotype.
- Tgfbr2 mutation model
- Tgfbr1M318R/+ model
- Smad3 knockout model
- Other models
Using state-of-the-art technology and the knowledge of our industry veterans, Protheragen's goal is to bring ideas from conception to reality faster. We intend to offer more than just a service; we thrive to be your research and development partner providing personalized support and building on our vast experience. Get in touch now and find out how we can help you with your research and development requirements.
References
- Schepers, Dorien et al. "A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3." Human mutation 39.5 (2018): 621-634.
- Lynch, Conor P et al. "Orthopaedic Management of Loeys-Dietz Syndrome: A Systematic Review." Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews 5.11 (2021): e21.00087.
For research use only, not for clinical use.