Alagille Syndrome (ALGS)
Alagille Syndrome is a genetic condition that affects multiple systems of the body such as the liver, heart, and other organs. That is why our company is focused on developing and improving diagnostics and therapeutics for better management of Alagille syndrome. Being your reliable partner for your Alagille syndrome research, we offer fully integrated solutions for all of your scientific needs.
Introduction to Alagille Syndrome
Alagille syndrome or Alagille-Watson syndrome is a multi-system genetic disorder with a low prevalence, affecting the liver, heart and few other organs. Alagille syndrome is an autosomal condition with an approximate prevalence of about 1 in 30,000.
Fig. 1 Notch signaling pathway. (Sanchez, Phillip, et al., 2021)Pathogenesis of Alagille Syndrome
Alagille syndrome is, to a great extent, caused by genetic changes that affect the order of the sequence of specific genes responsible for the maturation of various organs.
JAG1 and NOTCH2 Gene
Most cases of Alagille syndrome are due to JAG1 mutations. These mutations are mainly intragenic or deletions of JAG1. Extremely rare cases of Alagille syndrome stem from mutations in the NOTCH2 gene, specifically from missense mutations.
Notch Signaling Pathway
The intercellular communication and development of the embryo relies heavily on the JAG1 and NOTCH2 genes. Mutations of these genes lead to problems in the Notch signaling pathway which in turn leads to developmental issues especially concerning the bile ducts, heart, spine formation as well as the facial skeletal structure.
Types of Alagille Syndrome Therapy
Targeted Therapy
Searching for different compounds that interfere with the bile acids synthesis as well as target Notch signaling pathway is highly active. Improving liver function while reducing cholestasis and cardiac impairment is the main aim of these therapies. For instance, some γ-secretase inhibitors that change the modulation of Notch receptor processing are being examined.
Gene Therapy
Technologies like CRISPR-Cas9 gene editing are being investigated to fix the genetic mutations behind the Alagille syndrome. Normal cellular activity and symptoms for Alagille Syndrome can be managed through gene therapy with the help of precisely cutting the defective genes.
Our Services
Our company has pioneered research on the therapeutics of rare diseases and committed scientists working within our firm has created advanced platforms for the explication of the complexity of rare diseases, including Alagille syndrome.
Our research platforms
To meet the requirements for early detection and diagnosis of Alagille Syndrome, our company provides diagnostic development services. Alagille syndrome, an animal models, can be constructed in different species including mice, pigs, and zebrafish. The elaboration of these models allows our clients to perform safety evaluation of the drug safety evaluation and pharmacokinetics study of the substances.
Animal Models of Alagille Syndrome
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| Our company specializes in employing various genetic manipulation techniques, including gene knockouts and knock-ins, to introduce disease-causing mutations into animal models. To replicate the genetic abnormalities observed in individuals with Alagille syndrome (ALGS), our scientists perform gene knockout experiments in mice, effectively eliminating specific targeted genes. Furthermore, we utilize knock-in technology to insert specific mutations into the genomes of animal models, accurately reproducing the characteristics of human ALGS. | |||
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| Optional Species | Mice, Pigs, Zebrafish, Others | ||
Executive summary and selection of some interviews were conducted with a sizeable amount of respondents, and their comments were recorded in light of Alagille syndrome therapeutics development and research. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Sanchez, Phillip, et al. "Therapeutics development for Alagille syndrome." Frontiers in Pharmacology 12 (2021): 704586.
- Andersson, Emma R., et al. "Mouse model of Alagille syndrome and mechanisms of Jagged1 missense mutations." Gastroenterology 154.4 (2018): 1080-1095.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.