Alport Syndrome
Alport syndrome is a rare genetic disorder that manifests as a debilitating combination of kidney disease, hearing loss, and eye abnormalities. It is caused by mutations in genes encoding type IV collagen, a key component of the basement membrane in the kidneys, ears, and eyes. Our company stands at the forefront of advancements in the field of rare diseases, offering a comprehensive suite of services covering genetic analysis and disease modeling to therapeutic development.
Overview of Alport Syndrome
With a prevalence ranging from 1 in 5000 to 1 in 50,000 individuals, Alport syndrome affects both males and females, with an X-linked inheritance pattern being the most common. The syndrome can present in childhood or later in life, and its severity can vary widely among individuals. Common symptoms include blood in the urine (hematuria), proteinuria, progressive kidney dysfunction, high-frequency hearing loss, and ocular abnormalities such as lens dislocation and retinopathy.
Fig.1 Symptoms and GBM features observed in Alport syndrome. (Gregorio, V., et al., 2023)
Pathogenesis of Alport Syndrome
Alport syndrome is primarily caused by mutations in genes encoding type IV collagen, namely COL4A3, COL4A4, and COL4A5. Type IV collagen is essential for maintaining the structural integrity of the basement membrane in the kidneys, ears, and eyes. Mutations in these genes disrupt the formation and function of type IV collagen, leading to basement membrane abnormalities, impaired filtration in the kidneys, and progressive renal damage.
Fig.2 Type IV collagen from gene to protein trimerization to disease. (Gregorio, V., et al., 2023)Biomarkers Development of Alport Syndrome
Genetic testing by DNA sequencing technologies, such as next-generation sequencing plays a crucial role in confirming the diagnosis, identifying the specific genetic mutations, and determining the mode of inheritance. In addition, biomarkers can also provide information about the presence, severity, or progression of a disease, there are some potential biomarkers commonly associated with Alport syndrome.
- Vascular endothelial growth factor A
- High motility group box 1
- Epidermal growth factor
- Urinary monocyte chemoattractant protein-1
- Transforming growth factor beta 1
- Urinary podocin
Therapeutics Development of Alport Syndrome
| Agents | Types | Mechanism | Research Phase |
|---|---|---|---|
| Sparsentan | Small molecule inhibitor | Dual endothelin angiotensin receptor antagonist | Phase II trials |
| Atrasentan | Small molecule inhibitor | Endothelin A receptor antagonist | Phase II trials |
| ELX-02 | Aminoglycoside analog | Correct nonsense variants | Phase II trials |
| R3R01 | Lipid-modifying drug | A novel lipid-modifying agent | Phase II trials |
| Hydroxychloroquine sulfate (HCQ) | Small molecule drug | Suppressed the activation of toll-like receptors on the surface of endosomes | Phase II trials |
| Bardoxolone Methyl | Small molecule drug | Activation of Nrf2 and inhibition of NF-κB | Phase III trials |
| Exon skipping therapy | Gene therapy | Restore gene function | Preclinical research |
Our Services
With an unwavering commitment to the study and understanding of rare diseases, we possess animal models and therapeutic development platform that enables us to provide comprehensive services tailored to the unique needs of researchers in this field.
Therapy Development Platforms
Animal Models of Alport Syndrome
Animal models of Alport syndrome play a crucial role in advancing our understanding of the disease, elucidating its pathogenesis, and testing potential therapeutic interventions. Our company can provide a variety of animal models to help you develop targeted therapies and advance personalized drug for individuals affected by Alport syndrome.
Genetic engineering techniques such as CRISPR/Cas9 are used to create animal models of Alport syndrome that closely mimic specific genetic mutations found in human individuals.
Optional Models: Col4a3tm1Jhm model; Col4a5em1Keha model; Col4a4bwk model, etc.
Optional Species: Mice, Rats, Zebrafish, Non-Human Primates, Others
Our multidisciplinary team of experts combines cutting-edge scientific knowledge with state-of-the-art technologies to deliver innovative solutions and insights. We provide comprehensive services including pharmacokinetic studies and drug safety evaluation, to promote the understanding, diagnosis, and therapy of rare diseases.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Gregorio, Vanessa De et al. "Alport Syndrome: Clinical Spectrum and Therapeutic Advances." Kidney medicine 5.5 (2023): 100631.
- Gomes, Ana Marta et al. "Potential Renal Damage Biomarkers in Alport Syndrome-A Review of the Literature." International journal of molecular sciences 23.13 (2022): 7276.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.