Glycogen Storage Disease Type III (GSDIII)
Glycogen storage disease type III (GSDIII), or Cori disease, is an uncommon hereditary metabolic disorder that affects the ability to metabolize glycogen. Our company is a leader in the field of rare disease research, especially in GSDIII. We provide fully customized and integrated services for researchers and scientists in this particular field.
Overview of GSDIII
The occurrence of GSDIII is 1 in 100,000 births and is caused by a lack of the enzyme amylo-1,6-glucosidase (also known as the glycogen debranching enzyme). This enzyme is very important in the process of yielding glucose from glycogen for energy. Some of the GSDIII symptoms that those affected might show are hypoglycemia (low blood sugar), hepatomegaly (abnormally enlarged liver), weakness of muscle, and arrested development.
Fig.1 GSD can lead to long-term liver damage. (Pursell, N., et al., 2018)Pathogenesis of GSDIII
Associated with the previous condition, this disorder is genetically inherited and follows the autosomal recessive path due to mutations in the subunit genes of the AGL that synthesizes the glycogen debranching enzyme. The GSDIII individuals were found to have abnormal structures of glycogen in the liver and muscles as a result of too much accumulation of excessive, un-degraded glucose molecules due to a deficiency of the glycogen debranching enzyme. This abnormal glycogen structure is known to impede its catabolism into glucose. Thus, individuals suffering from this disorder face an inadequate supply of glucose, which is the most important energy source.
Fig.2 Glycogen metabolism. (Wicker, C., et al., 2023)Diagnostics Development of GSDIII
Analysis of Enzyme Activity
The primary method of confirming diagnosis of GSDIII involves a liver biopsy GSDIII and determining the severity of its manifestation is confirmed through the debranching enzyme glycogenolysis analysis.
Molecular Diagnosis
Through GENE mutations analysis for AGL gene alterations, it is possible to describe the changes affecting the enzyme debranching of glycogen as which serves as the basis for ascertaining the diagnosis reduction and discrimination of various forms of types of GSD III
Therapeutics Development of GSDIII
| Types | Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Gene therapy | lipid-nanoparticle-mediated RNAi gene silence | Inhibition of glycogen synthase 2 | Glycogen synthase 2 | Preclinical research |
| Dietary modifications | Maïzena® | Supplementation of raw cornstarch | Long-acting starch | Approved |
| Glycosade® | Supplementation of raw cornstarch | Long-acting starch | Approved | |
| Cardiac failure therapy | ACE inhibitors | Inhibition of angiotensin-converting enzyme | ACE | Approved |
| beta-blockers | Binding to beta-adrenergic receptors to inhibit their activation | beta-adrenergic receptors | Approved |
Our Services
Considering the rarity of the disease, the research process, which includes genetic testing, development of GSDIII animal models, and therapeutic, can prove to be intricate. However, our dedicated team of scientists and researchers is adept at providing guidance and support through all the stages of the process.
Platforms of GSDIII Therapy Development
Animal Models of GSDIII
A full understanding of the mechanism of the animal and for its accurate evaluation of new methods of therapeutic and testing for therapeutics, as well as testing for their use, is the primary purpose of animal models which are essential for studying the pathogenesis and developing new potential therapeutics for disease GSD III. Our company has developed a considerable number of disease GSD III models.
Genetic engineering techniques have been employed to create animal models of GSDIII. These models involve modifying the animal's genome to introduce mutations in the AGL gene.
Optional Models: Agltm1a(EUCOMM)Wtsi model; Aglem1Cya model, etc.
Why Choose US?
By providing a comprehensive suite of services including pharmacokinetic studies and biosafety evaluation, we aim to deliver innovative solutions that accelerate scientific discoveries and improve individual outcomes.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Wicker, Camille et al. "French recommendations for the management of glycogen storage disease type III." European journal of medical research 28.1 (2023): 253.
- Pursell, Natalie et al. "Inhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases." Molecular therapy: the journal of the American Society of Gene Therapy 26.7 (2018): 1771-1782.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.