Urea Cycle Disorders
Urea cycle disorders represent a group of genetic disorders that arise from deficiencies in enzymes crucial to the urea cycle, resulting in the build-up of toxic levels of ammonia in the bloodstream. Our company stands out in the realm of rare diseases like urea cycle disorders by offering comprehensive one-stop services tailored to researchers and scientists in this specialized field.
Overview of Urea Cycle Disorders
The urea cycle, a vital series of biochemical reactions that take place in the liver, plays a crucial role in the metabolism of proteins by converting ammonia, a byproduct of this process, into urea. Urea is then excreted from the body through urine, preventing the toxic buildup of ammonia levels in the bloodstream. However, disruptions in this cycle due to genetic mutations can lead to a group of disorders known as urea cycle disorders, affecting approximately 1 in 8,200 to 1 in 52,000 live births.
Fig.1 MRI of the brain and MRA from the individual. (Panichsillaphakit, E., et al., 2022)
Pathogenesis of Urea Cycle Disorders
Urea cycle disorders represent a group of genetic disorders arising from deficiencies in one of six enzymes or two carriers essential for eliminating ammonia from the body. Deficiencies in these enzymes lead to the accumulation of ammonia, which can result in serious neurological symptoms including vomiting, lethargy, seizures, developmental delays, and even coma, and can be life-threatening if not managed properly.
Fig.2 Characteristics of different urea cycle disorders. (Sen, K., et al., 2022)Diagnostics Development of Urea Cycle Disorders
Biochemical Testing
Biochemical testing offers essential insights into diagnosing urea cycle disorders by analyzing various parameters, including measuring ammonia levels, amino acids, and other metabolites.
Genetic Testing
Genetic testing is a pivotal method to confirm the diagnosis of urea cycle disorders by identifying mutations in the genes linked to the urea cycle enzymes, helping precisely pinpoint the genetic abnormalities.
Therapeutics Development of Urea Cycle Disorders
| Types | Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Small molecule drugs | L-carnitine | Restore mitochondrial respiration | CRAT | Approved |
| Sodium benzoate | Remove nitrogen | DAAO | Approved | |
| CARBAGLU® | Restore urea cycle function in inherited CPS1 deficiency | CPS1 | Approved | |
| Cell therapy | Human Heterologous Liver Cell therapy | Supply a sufficient amount of healthy liver cells to compensate for the metabolic defect | / | Phase III trials |
| Gene therapy | DTX301 | OTC gene transfer | OTC | Phase III trials |
| CRISPR/Cas9 | Correct missense mutations | OTC | Preclinical research | |
| LNPs-mRNA | Delivery of ARG1 mRNA by liver-targeted nanoparticles | ARG1 | Preclinical research | |
| ARCT-810 | Promote normal expression of function OTC enzymes | OTC | Phase II trials |
Our Services
We excel in providing a holistic approach to support research endeavors, from disease mechanism research to innovative therapeutic development. With our animal models and therapeutic development platform, we can accelerate discoveries, enhance understanding, and facilitate the development of innovative therapies for rare diseases.
Therapeutics Development Platforms
Animal Models of Urea Cycle Disorders
Animal models play a crucial role in studying urea cycle disorders to understand disease mechanisms, test potential therapeutics, and develop new therapies. Our company provides various animal models for you to investigate the pathophysiology of urea cycle disorders, test novel therapy strategies, and evaluate the efficacy of interventions.
The models are created through genetic engineering techniques such as CRISPR/Cas9 to mimic the genetic mutations associated with urea cycle disorders.
| Disease types | Optional Models |
|---|---|
| Carbamoylphosphate synthetase I (CPS1) Deficiency | Cps1tm1Mw model; Cps1em1Gpt model, etc. |
| Ornithine transcarbamylase Deficiency (OTCD) | Otcspf model; Otcspf-ash model, etc. |
| Argininosuccinate synthetase (ASS1) Deficiency | Ass1tm1Bay model; Ass1fold model, etc. |
| Argininosuccinate Lyase (ASL) Deficiency | Asltm1Brle model; Aslem1Cya model, etc. |
| Arginase (ARG1) Deficiency | Arg1tm1Pmu model; Arg1em1Cya model, etc. |
| N-acetyl glutamate synthetase (NAGS) Deficiency | Nagsem2Cya model, etc. |
Why Choose Us
Our team of experts offers support and guidance, ensuring that researchers have access to the latest tools and expertise needed to make significant strides in disease research. Our advantages lie in our ability to accelerate the research process by offering a wide range of services such as pharmacokinetic studies and drug safety evaluation.
If you are interested in our services, we invite you to contact us for detailed insights and comprehensive quotations.
References
- Matsumoto, Shirou et al. "Urea cycle disorders-update." Journal of human genetics 64.9 (2019): 833-847.
- Sen, Kuntal et al. "Fifteen years of urea cycle disorders brain research: Looking back, looking forward." Analytical biochemistry 636 (2022): 114343.
- Duff, Claire et al. "Gene therapy for urea cycle defects: An update from historical perspectives to future prospects." Journal of inherited metabolic disease 47.1 (2024): 50-62.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.