Wiskott-Aldrich Syndrome (WAS)
Wiskott-Aldrich syndrome manifests as aberrant immune system function (immunodeficiency), eczema (a skin disorder marked by inflamed patches of red, irritated skin), and diminished blood clotting ability. Specialized drug and therapy development services are essential to enhance and expedite Wiskott-Aldrich syndrome research. Our company is well-equipped to address your drug and therapy development requirements in Wiskott-Aldrich syndrome therapy.
Introduction to Wiskott-Aldrich Syndrome
- Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disorder characterized by immunodeficiency, eczema, and thrombocytopenia.
- The estimated incidence of WAS ranges from 1 in 100,000 to 1 in 250,000 live male births, making it one of the less common primary immunodeficiency disorders.
- WAS remains a challenging condition to manage due to its variable presentation and potential for life-threatening complications.
Fig. 1 Schematic representation of the WAS gene exon structure and protein domains. (Massaad, M.J., et al., 2013)Pathogenesis of Wiskott-Aldrich Syndrome
The pathogenesis of Wiskott-Aldrich Syndrome involves multiple immune cell dysfunctions: T-cells and antigen-presenting cells (APC) show impaired priming and activation, leading to defective T-cell responses. B-cells are also affected due to dysfunctional germinal center reactions and the absence of marginal zone B cells, contributing to impaired immune responses. Additionally, WAS is associated with thrombocytopenia due to both the intrinsic short lifespan of WAS platelets and autoimmune mechanisms, with some newly formed platelets getting trapped in the bone marrow.
Fig. 2 Mechanisms of disease in WAS. (Ferrua, F., et al., 2020)Diagnosis Development of Wiskott-Aldrich Syndrome
Genetic testing plays a crucial role in confirming the diagnosis of WAS. It involves identifying mutations in the WAS gene, which encodes the Wiskott-Aldrich syndrome protein (WASp). This protein is vital for cell actin cytoskeleton assembly and influences various immune functions. Advanced diagnostic methods now include next-generation sequencing, allowing for a comprehensive examination of the WAS gene to detect known and novel mutations .
Therapy Development of Wiskott-Aldrich Syndrome
Gene therapy represents one of the most promising frontiers in the therapy of WAS. This approach involves the correction of the genetic defect at the source by introducing a functional WAS gene into the individual's cells. Recent advancements have seen the use of lentiviral vectors to safely and effectively deliver a correct copy of the WAS gene to individual-derived hematopoietic stem cells.
Cell therapies for WAS primarily involve hematopoietic stem cell transplantation (HSCT). HSCT can provide a curative therapy by replacing the defective immune system with one derived from healthy donor stem cells. Success rates vary, but when successful, HSCT can correct the underlying immune deficiencies associated with WAS. Recent research use matched unrelated donors and refining conditioning regimens to reduce graft-versus-host disease and other complications.
While monoclonal antibodies are not directly used to treat the genetic root of WAS, they are integral in managing complications and symptoms associated with the disease. Monoclonal antibodies targeting inflammatory cytokines or modulating immune responses can be used to manage autoimmunity and inflammatory conditions that many WAS iindividuals experience. Rituximab, which targets CD20 on B cells and can be used to control autoimmune manifestations.
Small molecule drugs are designed to modulate biological pathways at a molecular level. For WAS, the focus is often on drugs that can enhance immune system functionality or ameliorate symptoms of the disease. An example includes the use of drugs that modulate signal transduction pathways involved in T-cell and B-cell receptor signaling. Research into pharmacological modulation of WASp activity or its downstream effects holds potential.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Wiskott-Aldrich syndrome therapy strategies and ensure robust support throughout the process.
Platforms of Wiskott-Aldrich Syndrome Therapy Development
Animal Models of Wiskott-Aldrich Syndrome
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Chemical Induced Models | ||
| We provide diverse model choices customized to meet specific research needs related to Wiskott-Aldrich syndrome. | ||
| Optional Models |
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| Radiation Induced Models | ||
| Radiation induced models rely on the exposure of animals to ionizing radiation to induce changes that mimic the disease's characteristics in humans. | ||
| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Wiskott-Aldrich syndrome. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Massaad, M.J., et al., "Wiskott-Aldrich syndrome: a comprehensive review." Ann N Y Acad Sci, (2013). 1285: p. 26-43.
- Ferrua, F., et al., "Gene therapy for Wiskott-Aldrich syndrome: History, new vectors, future directions." J Allergy Clin Immunol, (2020). 146(2): p. 262-265.
- Thrasher, A.J., "New insights into the biology of Wiskott-Aldrich syndrome (WAS)." Hematology Am Soc Hematol Educ Program, (2009): p. 132-138.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.