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 are important for the proper and faster performance of ADA-SCID research. Our company can assist you in the formulation and development of an ADA-SCID therapy.
Introduction to ADA-SCID
Individuals suffering from severe adenosine deaminase SCID cannot defend themselves against viral, bacterial, and fungal infections. Patients suffering from severe combined immunodeficiency due to the deficiency of adenosine deaminase deficiency manifests symptoms before six months of age. The earliest symptoms of severe adenosine deaminase SCID may consists of pneumonia, chronic diarrhea, extensive skin rashes, growth retardation, and/or developmental delays. Some individuals suffering from adenosine deaminase deficiency may develop symptoms at a later stage of life.
Pathogenesis of ADA-SCID
SCID Resulting from Deficiency of Adenosine Deaminase (ADA) has an altered immunological functioning due to mutation in ADA gene leading to non-functioning ADA enzyme. It results in purine metabolism disorder and resultant toxic dAdo derivate causing damage to lymphocytes. The resultant lymphopenia causes severe compromise of T and B cells differentiation and function leading to severe immunodeficiency associated with recurrent infection and failure to thrive. Stem cell insertion or enzyme substitution infusion are two available treatment options that are believed to ameliorate immune system deficiency.
Fig.1 Biochemistry of adenosine deaminase-deficient severe combined immune deficiency (ADA SCID). (Bradford, K.L., et al., 2017)Diagnostic Development of ADA-SCID
Incremental improvements have been observed in the diagnostics development of ADA-SCID, especially with the introduction of blood tests which take on the form of prospective screening for newborn babies. Confirmatory tests are performed by determining the enzyme activity of ADA and mutation of the ADA gene by molecular genetic methods such as enzyme assays or DNA sequencing. Improved technologies characterized by such methods as Next generation sequencing (NGS) which have systematically improved the efficacy and efficiency of genetic testing for ADA-SCID diagnosis by analyzing the whole sequence of the ADA gene for the specific change and ultimately aiding in accurate 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
We dedicate ourselves to working closely with clients, thus allowing us to develop therapies for ADA-SCID that are innovative and effective. Our staff works around the clock to develop strategies that meet your goals so that you are assisted and taken care of at every turn.
Platforms of ADA-SCID Therapy Development
Animal Models of ADA-SCID
We have developed the expertise needed to create and use relevant animal models that are important for the studies and mimic the appropriate disease and therapeutic response. Such models allow us to estimate the safety and effectiveness of the possible therapies.
Besides these models, our complete solutions include other models for testing some pathways and molecular targets.
| 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. | ||
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| 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 ADA-SCID. | ||
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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.