Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Protheragen delivers end-to-end solutions for aHUS, leveraging cutting-edge insights into complement dysregulation and genetic drivers to combat this life-threatening thrombotic microangiopathy.
Overview of Atypical Hemolytic Uremic Syndrome
aHUS is a rare, genetic thrombotic microangiopathy caused by uncontrolled complement activation due to mutations in CFH, CFI, CFB, C3, or MCP. Affecting 1–2 per million annually, it manifests as microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Without prompt intervention, 50% of patients progress to end-stage kidney disease (ESKD). Early diagnosis and targeted therapies are critical to preserving renal function.
Pathogenesis of Atypical Hemolytic Uremic Syndrome
aHUS is driven by dysregulated complement activation due to mutations in complement regulatory genes (e.g., CFH, CFI, C3) or autoantibodies, leading to uncontrolled alternative pathway activity. Persistent formation of the membrane attack complex (MAC) on endothelial cells triggers microvascular thrombosis, thrombocytopenia, and hemolytic anemia. Genetic susceptibility combined with environmental triggers (e.g., infections) exacerbates systemic endothelial injury and renal failure.
Fig.1 Alternative pathway of complement. (Raina
et al., 2019)
Therapeutics Development for Atypical Hemolytic Uremic Syndrome
| Therapeutic Strategy |
Mechanism |
Key Findings/Evidence |
Development Stage |
| Pegcetacoplan (APL-2) |
C3 inhibitor (targets C3 cleavage) |
Phase II: 45% reduction in proteinuria in C3G/aHUS overlap patients |
Phase III |
| AMY-101 (Cp40 analog) |
Oral C3 inhibitor |
Phase I: >90% C3b inhibition; no dose-limiting toxicity |
Phase II |
| IONIS-FB-LRx (ASO) |
Suppresses factor B production |
Phase II: 70% reduction in alternative pathway activity in primates |
Phase II |
| CRISPR-Cas9 Editing |
Corrects CFH mutations in iPSCs |
80% functional recovery of complement regulation in preclinical models |
Preclinical |
| Liver Transplant + Eculizumab |
Surgical replacement + short-term C5 blockade |
92% 5-year relapse-free survival in CFH mutation carriers |
Clinical Practice |
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.
Our Services
Protheragen is a comprehensive preclinical service provider dedicated to the therapeutic development for Atypical Hemolytic Uremic Syndrome. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture the profound renal and systemic features of this inherited and complement-mediated disorder, supporting mechanism-based drug discovery for its severe clinical manifestations.
Therapeutic Development Platforms for aHUS
Disease Models Development for aHUS
Protheragen provides specific and robust disease models to accelerate preclinical research on aHUS. Our platform integrates cell-based models, kidney organoids, and animal models. These are essential for dissecting the impact of complement gene mutations, understanding the mechanisms of complement dysregulation, and testing novel therapeutic interventions for kidney protection and systemic TMA resolution.
Cell-based & Organoid Models
- CFH-mutated endothelial cell model
- iPSC-derived complement-dysregulated blood cells
- Microvascular thrombosis-on-a-chip
- Complement activation co-culture system
Animal Models
- CFH (Complement Factor H) knockout mice
- C3-overexpressing transgenic rats
- CD46 (MCP) deficient mouse model
- Thrombomodulin (THBD) mutant zebrafish
Protheragen offers end-to-end preclinical development solutions specifically designed for research in severe congenital and acquired renal disorders like aHUS. We specialize in custom disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from initial discovery through to preclinical validation.
If you are interested in our services, please don't hesitate to contact us.
References
- Raina, R., et al. "Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment." Ther Apher Dial 23.1 (2019): 4-21.
- Yoshida, Y., et al. "Pathogenesis of Atypical Hemolytic Uremic Syndrome." J Atheroscler Thromb 26.2 (2019): 99-110.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
