Von Hippel-Lindau Syndrome (VHL)
Von Hippel-Lindau syndrome (VHL) is a rare genetic disorder that causes the growth of noncancerous tumors in various parts of the body. Our company stands at the forefront, armed with a distinguished research corps and cutting-edge technological advancements. Which can help you to illuminate the pathogenesis of VHL, catalyze the advancement of tailored therapeutic modalities, and march steadfastly towards pioneering breakthroughs in the intricate domain of VHL diagnostics and therapeutic strategies.
Introduction to VHL
Von Hippel-Lindau syndrome (VHL) is a rare genetic disorder that affects around 1 in 35,000 individuals. One aspect of understanding VHL is the potential development of pheochromocytoma or renal cell carcinoma, which serves as a key indicator of the condition. Through meticulous research and observation, four distinct VHL phenotypes have been identified: type 1, type 2A, type 2B, and type 2C. These classifications provide valuable insights into the diverse manifestations of VHL.
Pathogenesis of VHL
VHL is caused by mutations in the VHL gene located on chromosome 3 (3p25-26), which is responsible for producing a protein that helps regulate cell growth. The exact mechanism by which VHL gene mutations lead to tumor formation is thought to involve dysregulation of hypoxia-inducible factors (HIFs), which control the response to low oxygen levels in cells (Fig.1). One crucial aspect of VHL research revolves around the regulation of hypoxia-induced mRNA expression of vascular endothelial growth factor (VEGF) by the VHL gene.
Fig.1 VHL protein functions: HIF independent and HIF dependent. (Glasker, S., et al., 2020)Diagnostics Development of VHL
To identify genetic mutations in the VHL gene and accurately diagnose VHL, comprehensive genetic testing approaches such as single-gene testing, multigene panel, and advanced sequencing technologies like whole genome sequencing (WGS), whole exome sequencing (WES), and next-generation sequencing (NGS) are utilized. These methods help in pinpointing specific genetic abnormalities associated with VHL.
Therapeutics of VHL
Small Molecule Drug Therapy
These inhibitors work by targeting specific pathways involved in the development of VHL disease, such as targeting HIF2 (belzutifan), EglN prolyl hydroxylase (daprodustat, vadadustat), and tyrosine kinase (sunitinib, pazopanib, and sorafenib, etc.). Which can help to slow down the progression of VHL disease and improve symptoms in individuals.
Monoclonal Antibody Therapy
Anti-VEGF monoclonal antibodies, such as bevacizumab, ranibizumab, and pegaptanib, are also used in the therapeutic of VHL disease. Inhibiting the interaction between VEGF-A and its receptors (VEGFR1/2) prevents the formation and growth of blood vessels within the tumors, thereby resulting in reductions in tumor size and overall disease burden for VHL individuals.
Gene Therapy
Gene therapy methods for VHL aim to replace or repair the faulty gene to restore its normal function. Some of the gene therapy approaches include CRISPR/Cas9 gene editing, RNA interference (RNAi), viral vectors, or other delivery methods to evaluate the safety and efficacy of gene therapy in VHL.
Our Services
Our company with cutting-edge technologies, and advancements in rare disease diagnosis and therapeutic, including the development of animal models and therapeutic platforms, which can support your research of VHL.
Platforms of VHL Therapy Development
Animal Models of VHL
Animal models of VHL are key to studying the genetic and molecular pathways involved in the disease and to test potential therapeutic strategies. With our advanced technology and expertise in genetic engineering, we can provide customized animal models tailored to your specific research need.
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| Genetic engineering techniques such as CRISPR/Cas9, transgenic approaches, or viral vector delivery can be used to introduce targeted mutations in the VHL gene in animals like mice, zebrafish, and rats to study the disease and potential therapeutic interventions. | ||
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| Xenograft Models | ||
| Xenograft models involve the transplantation of human VHL-associated tumor cells into immunodeficient mice. These models allow researchers to study the growth and behavior of human VHL-associated tumors in a controlled environment. | ||
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| Optional Species | Mice, Rats, Zebrafish, Others | |
These models can be used to test the efficacy of new drugs or gene therapies for VHL and to support pharmacokinetics analysis and drug safety evaluation. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Hudler, Petra, et al. "The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis." Genes 13.2 (2022): 362.
- Kaelin, William G Jr "Von Hippel-Lindau disease: insights into oxygen sensing, protein degradation, and cancer." The Journal of clinical investigation 132.18 (2022): e162480.
- Glasker, Sven, et al. "Von Hippel-Lindau Disease: Current Challenges and Future Prospects." OncoTargets and therapy 13 (2020): 5669–5690.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.