Ornithine Transcarbamylase Deficiency (OTCD)
Ornithine transcarbamylase deficiency (OTCD) stands as an intrinsic genetic disorder marked by the hindered function of the OTC enzyme, crucial in the elimination of surplus nitrogen from the body via the urea cycle. Engaging in pioneering strides within the realm of rare diseases, our company takes pride in delivering a spectrum of all-encompassing services tailored to the requisites of researchers and scientists.
Overview of OTCD
The prevalence estimates of OTCD hover between 1 in 14,000 to 1 in 80,000 live births, underscoring its nature as an X-linked disorder predominantly impacting males. However, females too can experience its effects. Primarily afflicting the liver, OTCD catalyzes the accumulation of ammonia, a hazardous substance, in the bloodstream. The condition's severity varies significantly, spanning from neonatal-onset with severe symptoms to late-onset featuring milder or even asymptomatic presentations.
Fig.1 Mitochondrial OTC in its metabolic context in liver and intestine. (Couchet, M., et al., 2021)Pathogenesis of OTCD
Encoded by the human OTC gene situated on the X-chromosome's short arm (Xp21.1), OTCD is associated with over 500 reported mutations in the OTC gene. This leads to a scarcity or total absence of functional OTC enzyme activity, resulting in the buildup of ammonia in the bloodstream. The accumulation of ammonia can trigger hyperammonemia, instigating neurological impairment, liver dysfunction, and potentially perilous complications.
Fig.2 Structure of human OTC. (Couchet, M., et al., 2021)Diagnostics Development of OTCD
Biochemical Tests
The assessment of ammonia levels and other metabolites such as orotic acid and glutamine, which are typically elevated in affected individuals.
Gene Detection
Detecting mutations in the OTC gene through DNA analysis, aiding in definitive diagnosis and the identification of specific genetic variants.
Therapeutics Development of OTCD
| Types | Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Gene therapy | AAV8-based OTC delivery | Provide successful OTC DNA and RNA delivery | OTC | Phase III trials |
| AAVLK03.hOTC | Increase the OTC enzyme activity | OTC | Phase I/II trials | |
| LNP hOTC mRNA | Lipid nanoparticle to deliver OTC mRNA | OTC | Phase I/II trials | |
| Genome editing | Corrected the mutation of OTC | OTC | Preclinical research | |
| Microbiological therapy | Synb1020 | An engineered E coli Nissle strain | Ammonia | Phase I/II trials |
| Supplements | Arginine / citrulline | Support the urea cycle and promote ammonia detoxification | Ammonia | Approved |
Our Services
Our comprehensive services amalgamate a plethora of expertise and resources, uniting a diverse team encompassing geneticists, molecular biologists, biochemists, and rare disease specialists. With the animal model and therapeutic development platform, we offer an integrated approach to research and discovery of OTCD.
Therapy Development Platforms
Animal Models of OTCD
Animal models play a pivotal role in unraveling the intricacies of OTCD and its underlying mechanisms. Our company offers diverse animal models for you to delve into the pathogenesis of OTCD, evaluate potential therapeutic avenues, and probe the ramifications of genetic and environmental determinants on disease progression.
Using gene editing techniques such as CRISPR/Cas9, researchers have generated animal models with mutations in the OTC gene. These models exhibit a show similarity to human OTCD, including hyperammonemia and liver dysfunction.
Optional Models: Otcspf-ash model; Tg(Otc)94Mori model; Otcspf model, etc.
Why Choose Us
Through an array of services encompassing pharmacokinetic studies and drug safety evaluations, we aim to accelerate scientific advancements in understanding, diagnosing, and treating OTCD.
If you are seeking reliable support and cutting-edge resources for your research endeavors, we invite you to engage with our team and explore the possibilities for collaboration. Contact us today to learn more about our services and how we can empower your research goals.
References
- Couchet, Morgane et al. "Ornithine Transcarbamylase - From Structure to Metabolism: An Update." Frontiers in physiology 12 (2021): 748249.
- Seker Yilmaz, Berna, and Paul Gissen. "Genetic Therapy Approaches for Ornithine Transcarbamylase Deficiency." Biomedicines 11.8 (2023): 2227.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.