Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical hemolytic uremic syndrome (aHUS) is an exceedingly uncommon, potentially fatal, progressive disorder frequently associated with a genetic predisposition. With our pioneering efforts in aHUS research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of aHUS. As your reliable partner in aHUS research, we offer unmatched support to fulfill your scientific research needs.
Introduction to aHUS
Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening condition marked by persistent and uncontrolled activation of the complement system, a vital component of the body's immune response. This disease is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body. The incidence of this disease is incredibly low, with approximately 2 cases per million individuals in the United States, as indicated by a study.
Fig. 1 Complement activation in atypical hemolytic uremic syndrome. (David Kavanagh, et al., 2014)Pathogenesis of aHUS
The pathogenesis of aHUS revolves around dysregulation in the complement system, leading to systemic thrombotic microangiopathy (TMA). The mechanisms underlying complement system dysregulation involve two factors.Gene Mutation
One of the primary mechanisms underlying aHUS is the presence of genetic mutations in complement regulatory proteins, such as factor H, factor I, or membrane cofactor protein (MCP). These mutations disrupt the delicate balance between complement activation and regulation, resulting in uncontrolled complement system activity.
Effects of Autoantibodies
Acquired neutralizing autoantibodies can also trigger aHUS by inhibiting the normal functioning of complement system components, notably anti-factor H antibodies. The dysregulated complement cascade leads to platelet activation, damage to endothelial cells, and the formation of blood clots in small blood vessels throughout the body.
Targets of aHUS Therapy
| Target | Description |
|---|---|
| Complement Factor H (CFH) and B (CFB) | CFH is a protein responsible for regulating and controlling the activity of the complement system, and CFB is one of the key factors in complement activation. In aHUS, mutations in the CFH and CFB genes lead to an imbalance in the complement system. Currently, drugs that inhibit CFH and CFB are under research. |
| Terminal Complement Pathway | Targeting the terminal complement pathway has been a primary focus in developing therapies for aHUS. Inhibitors of complement component C5, like eculizumab and ravulizumab, prevent the formation of terminal complement complexes, halting the downstream complement-mediated damage. |
Types of aHUS Therapy
Monoclonal Antibody Therapy
Eculizumab and ravulizumab are monoclonal antibodies that specifically target complement component C5. These medications have demonstrated significant improvements in outcomes for individuals with aHUS, reducing the risk of mortality and end-stage renal disease.
Plasma Exchange/Infusion Therapy
Plasma exchange and plasma infusion aim to remove complement components, including autoantibodies or other factors that contribute to complement dysregulation, while replenishing deficient regulatory factors. The therapeutics can provide immediate relief of symptoms and delay disease progression.
Our Services
Our company has established a comprehensive platform for developing rare disease diagnostics and therapies, encompassing small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. Through our dedicated platforms, we are fully devoted to advancing the development of innovative diagnostic tools and therapies for aHUS.
Animal Models of aHUS
By utilizing our specialized knowledge and experience, we can create animal models that closely mimic the pathophysiological features of aHUS. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
| Genetically Engineered Models | ||
| Our scientists employ genetic engineering techniques to generate transgenic or knockout animals with aHUS-related genetic alterations. Transgenic animals express mutated genes associated with aHUS, while knockout animals have specific complement regulatory genes intentionally deleted. These models aim to mimic the genetic abnormalities seen in aHUS individuals and investigate their effects on complement regulation and disease development. | ||
| Optional Models |
|
|
| Optional Species | Mice, Zebrafish, Non-human Primates (Baboons), Others | |
If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Kavanagh, David, Shreya Raman, and Neil S. Sheerin. "Management of hemolytic uremic syndrome." F1000Prime Reports 6 (2014).
- Leon, Juliette, et al. "Complement‐driven hemolytic uremic syndrome." American Journal of Hematology 98 (2023): S44-S56.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.