DiGeorge Syndrome
DiGeorge syndrome is due to a microdeletion in chromosome 22q11.2, which results in hypoplastic or dysmorphic function of the pharyngeal pouch system. Individuals with DiGeorge syndrome can have aberrations of development in the head/face, as well as in the heart outflow tract, and parathyroid organ and thymic tissue. Protheragen is one of the providers of research services and is making efforts to address the issues of rare diseases, cardiovascular DiGeorge syndrome included. Combining insightful scientific analysis with unique perspectives, we provide critical insights and services to develop products from design through marketing.
Introduction to DiGeorge Syndrome
DiGeorge syndrome is also known as a velocardiofacial syndrome and chromosome 22q11.2 deletion syndrome. It is thought to occur in 1/4000 births. Specific characteristics of 22q11.2 deletion syndrome such as congenital heart malformations, hypoparathyroidism, and hypoplasia/aplasia of the thymus arise from the failed development of the third and fourth pharyngeal pouches. 80% of the population of newborns with DiGeorge syndrome also have cardiac defects.
Fig.1 Genetics of DiGeorge syndrome. (Menghi, M., et al., 2023)Pathogenesis of DiGeorge Syndrome
The typical phenotype of DiGeorge syndrome microdeletion 22 hemizygous appears in 35% to 90% of the cases of DiGeorge syndrome. This deletion is due to abnormal chromosome breaking and remodeling during meiotic division involving low copy repeats (LCRs) within a region of chromosome 22q11.2. The majority of deletion from LCR22A-D is around 84% and is caused by the common 3Mb deletion. Among more than 30 genes participating in their development, T-Box transcription factor 1 (TBX1) is the most noteworthy when it comes to immune deficiency in DiGeorge syndrome.
Fig.2 DiGeorge syndrome signs and symptoms. (Menghi, M., et al., 2023)Therapeutics Development for DiGeorge Syndrome
| Drug Names | Targets | Mechanism of Action | Research Phase |
|---|---|---|---|
| Thymus Transplantation | T-cell | Reestablish T-cell immunity by implanting thymic tissue. | Approved |
| Vitamin B12 | / | Augment Tbx1 gene expression and partly rescues the phenotype resulting from a single functional copy of a gene. | Preclinical |
| Minoxidil | Lysyl hydroxylase | A lysyl hydroxylase inhibitor improved the cardiac outflow tract septation phenotype in Tbx1 mutant fetuses. | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen enables our partners with the latest technology, and a focus on the customer to be faster and more reliable in their pursuit of successful therapy development. We have expertise throughout the preclinical spectrum from the latest diagnostic platforms to the newest therapeutics, to model development. Our end-to-end solution not only improves the process of drug discovery but also expedites lab-to-bedside.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for DiGeorge Syndrome
Animal models are indispensable to further elucidate DiGeorge syndrome and allow researchers to investigate complex mechanisms and test therapeutic interventions while working in a controlled environment. We provide proprietary animal model development services designed to reflect the characteristics of the disease (including DiGeorge syndrome) to expedite testing and therapeutic discovery.
Genetically Engineered Animal Models
Genetic engineering animal models for DiGeorge syndrome, developed using cutting-edge techniques, precisely replicate specific genetic anomalies.
- Tbx1 mutation model
- Raldh2 mutation model
- LgDel mouse model
- Other models
Beyond your drug discovery needs, Protheragen's strong presence in pharmacokinetic studies and drug safety assessment affords you comprehensive preclinical perspectives and services. Our cross-discipline experts work closely with clients to speak to the opportunities and potential pitfalls in drug development. Should you wish any of our services, please do get in touch.
Reference
- Menghi, Michela et al. "Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome." International journal of molecular sciences 24.4 (2023): 4242.
For research use only, not for clinical use.