Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency (ADA-SCID)
Severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is an inherited condition that damages the immune system and is a common cause of severe combined immunodeficiency (SCID). Specialized drug and therapy development services are essential to enhance and expedite ADA-SCID research. Our company is well-equipped to address your drug and therapy development requirements in ADA-SCID therapy.
Introduction to ADA-SCID
People with SCID due to Severe combined immunodeficiency due to adenosine deaminase deficiency cannot fight off most types of infections, including bacterial, viral, and fungal infections. Most people with severe combined immunodeficiency develop symptoms before 6 months due to adenosine deaminase deficiency. The earliest symptoms of Severe combined immunodeficiency due to adenosine deaminase deficiency may include pneumonia, chronic diarrhoea, widespread skin rashes, slowed growth, and/or developmental delay. Some people with ADA deficiency may develop symptoms later in life.
Pathogenesis of ADA-SCID
SCID caused by Adenosine Deaminase (ADA) deficiency disrupts immune function due to mutations in the ADA gene, leading to a lack of functional ADA enzyme. This deficiency impairs purine metabolism, resulting in the toxic buildup of substances like deoxyadenosine (dAdo), which damages lymphocytes. The consequent lymphopenia severely compromises T and B cell development and function, resulting in profound immunodeficiency characterized by recurrent infections and failure to thrive. T therapeutics options typically include stem cell transplantation or enzyme replacement therapy to restore immune function.
Fig.1 Biochemistry of adenosine deaminase-deficient severe combined immune deficiency (ADA SCID). (Bradford, K.L., et al., 2017)Diagnostic Development of ADA-SCID
Significant progress has been made in the diagnostics development of ADA-SCID, notably with the emergence of blood tests as valuable tools for potential newborn screening. Confirmatory tests involve measuring ADA enzyme activity or identifying ADA gene mutations through molecular genetic testing, employing techniques like enzyme assays and DNA sequencing. Technological progress, notably next-generation sequencing (NGS), has significantly improved genetic testing accuracy and efficiency for ADA-SCID, enabling comprehensive analysis of the ADA gene and facilitating precise diagnosis and genetic counseling.
Therapy Development of ADA-SCID
small molecule drugs are typically focused on enzyme replacement to compensate for the lack of ADA activity. Pegademase bovine (Adagen) is an enzyme replacement therapy where a pegylated form of bovine ADA is administered to reduce the levels of toxic metabolites harmful to the immune system.
Cell therapies for ADA-SCID revolve around stem cell transplantation to restore immune system function. Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor is a preferred therapy and can be curative. For individuals without a matched sibling donor, stem cells from a parent or other partially matched donor can be used.
Monoclonal antibodies are less commonly a direct therapy option for ADA-SCID but are used in conjunction with other therapies. Antithymocyte Globulin (ATG) is used in the preparative regimen for HSCT to suppress the immune system and reduce the risk of rejection in stem cell transplantation.
Techniques range from using retroviral vectors in therapies like Strimvelis, which modify an individual's own cells ex-vivo, to employing cutting-edge in vivo editing tools like CRISPR/Cas9. This diversity in approaches not only enhances therapy efficacy but also broadens the potential to cure these hereditary conditions permanently.
Fig.1 Schematic representation of the key scientific and regulatory milestones in the clinical development of ADA‐SCID gene therapy, leading to its approval in the EU. (Aiuti, A., et al., 2017)Our Services
At our company, we prioritize a partnership-driven approach. We work together with our clients to develop innovative ADA-SCID therapies. Our team dedicates itself to crafting personalized strategies that align with your objectives, ensuring you are supported at every step.
Platforms of ADA-SCID Therapy Development
Animal Models of ADA-SCID
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.
| Non-Genetically Engineering Models | ||
| Our company specializes in delivering top-notch services to create NON-GEMs. We provide diverse model choices customized to meet specific research needs related to ADA-SCID. | ||
| Optional Models |
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| 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 ADA-SCID. | ||
| 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 resonate with you, we invite you to contact us whenever works best for you. Let's discuss customizing our solutions to align seamlessly with your objectives and aspirations.
References
- Aiuti, A., et al., "Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced treatment medicinal products." EMBO Mol Med, (2017). 9(6): p. 737-740.
- Bradford, K.L., et al., "Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations." J Clin Immunol, (2017). 37(7): p. 626-637.
- Secord, E. and Hartog, N.L., "Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID)." Ther Clin Risk Manag, (2022). 18: p. 939-944.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.