Wiskott-Aldrich Syndrome (WAS)
Symptoms of this condition include marked dysfunction of the immune system (immunodeficiency), eczema (allergic dermatitis), and blood clotting disorders. Drawing from this, it is evident that there is a need for differentiated drug and therapy development services that would increase Wiskott Aldrich syndrome research efforts. Our company is well positioned to meet your needs for drug and therapy development for Wiskott Aldrich syndrome.
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 dysfunctions of multiple immune components are at the center of Wiskott-Aldrich Syndrome pathogenesis, with T-lymphocytes and antigen presenting cells (APC) displaying insufficient priming and activation, which leads to defective T-cell responses. Immune responses are further compromised due to dysfunctional germinal center reactions and no marginal zone B cells, which lastly affect B-cells. In addition, thrombocytopenia with WAS is partially explained by the autoimmune processes combined with the short life span intrinsic to WAS platelets, which leads to some of the newly formed platelets getting sequestered in the bone marrow.
Fig. 2 Mechanisms of disease in WAS. (Ferrua, F., et al., 2020)Diagnosis Development of Wiskott-Aldrich Syndrome
The diagnosis of WAS is primarily confirmed through genetic testing on the WAS gene. This gene is responsible for the production of WASp, the protein that enables the assembly of actin cytoskeleton in a cell and regulates several immune functions. The WAS diagnosis is further facilitated by next generation sequencing, which allows for more thorough testing of known and unknown mutations within the WAS gene.
Therapy Development of Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome (WAS) therapy would most likely benefit from current advances in gene therapy. This strategy indicates addressing the genetic defect at its source by inserting a functional WAS gene into the individual's cells. Recent studies showed that lentiviral vectors could be used to transduce individual-derived hematopoietic stem cells with the WAS gene without compromising safety or efficacy.
The predominant cell therapy for WAS is hematopoietic stem cell transplantation (HSCT). HSCT can cure the disease by providing a healthy immune system based on the individual's peripheral blood stem cells. The results are variable, but with positive outcomes, HSCT does resolve the immune problems that are the root cause of WAS. More recent studies involve the use of matched unrelated donors and modifying conditioning regimens in order to lessen the incidence of graft-versus-host disease and other problems.
As much as monoclonal antibodies don't specifically focus on treating the WAS hereditary aspect, they are essential in the therapeutic of the various complications and symptoms of the disorder. Monoclonal antibodies that neutralize inflammatory cytokines or alter immune responses can be used to treat autoimmunity and inflammatory problems many WAS individuals face. Controls autoimmune manifestations with Rituximab that binds to CD20 B cells.
Small molecule drugs are developed to change biological activities of the pathway on the molecular level. When it comes to WAS, the consideration is frequently given to drugs that make the immune system more effective or lessen the disease's symptoms. An example includes the employing of medications that alter the activity of signal transduction processes of the T and B lymphocyte receptors. Blocking, or at least reducing, the activity of WASp or its downstream effects should be therapeutically efficient.
Our Services
The operations of our company are based on the retention on partnerships. We work closely with the customers in developing unique and comprehensive Wiskott-Aldrich syndrome therapy designs and provide adequate follow up assistance.
Platforms of Wiskott-Aldrich Syndrome Therapy Development
Animal Models of Wiskott-Aldrich Syndrome
We possess the necessary skills and resources to create and use animal models that closely resemble the disease and its response to therapeutic. These models help us assess the specific required safety and effectiveness of a proposed therapeutic.
| 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, 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.