Calpainopathy
Calpainopathy is a disease characterized by muscle atrophy and weakness. Our company boasts a highly skilled team of researchers and scientists who possess extensive expertise in the study of calpainopathy. This expertise serves as the cornerstone for the development of groundbreaking diagnostic tools and therapeutic drugs. As your reliable and trusted partner, we offer a comprehensive suite of services tailored to meet your specific scientific research requirements.
Introduction to Calpainopathy
Calpainopathy, also known as autosomal recessive limb-girdle muscular dystrophy (LGMD), is a genetic disorder affecting the muscles of the hip girdle and shoulder girdle. There are various subtypes of calpainopathy, including pelvic-femoral LGMD, scapulohumeral LGMD, and HyperCKemia. Calpainopathy is a rare condition, affecting approximately 1 in every 80,000 individuals.
Fig. 1 Illustration of the pathological features of CAPN3 deficiency in the skeletal muscle. (Lasa-Elgarresta, et al., 2019)Pathogenesis of Calpainopathy
The pathogenesis of calpainopathy revolves around the mutations in the CAPN3 gene, responsible for coding the essential protein calpain-3.
Calpain-3 Protein
Calpain-3 plays a dual role as a protease and a structural protein, primarily found in muscle tissues. Its protease function involves the cleavage of sarcomere and cytoskeletal proteins, contributing to muscle remodeling. Additionally, calpain-3 is essential for stabilizing triad protein complexes involved in calcium regulation and excitation-contraction coupling.
CAPN3 Gene
Mutations in the CAPN3 gene disrupt the normal function of calpain-3, impairing its ability to properly regulate muscle protein turnover and maintenance. In addition, calcium channels such as ryanodine receptor (RYR1) and dihydropyridine receptor (DHPR) are also impaired. Disruption of the calcium regulation causes degeneration and loss of muscle tissue, leading to calpainopathy.
Diagnostics Development of Calpainopathy
Accurate and early diagnosis of calpainopathy is critical to improving therapeutic outcomes for affected individuals. The main diagnostic methods are as follows:
- Genetic testing is the gold standard for confirming the presence of CAPN3 mutations.
- Muscle biopsy helps identify the presence of calpain-3 and other relevant proteins in muscle tissue.
- Elevated serum creatine kinase levels may be observed in the early stages of the disease.
Therapeutics Development of Calpainopathy
- Targets of Calpainopathy Therapy Development
| Target | Description |
|---|---|
| Calpain-3 (CAPN3) | Restoring or enhancing the activity of calpain-3 holds promise as a potential therapeutic strategy. Advanced gene editing technologies like CRISPR-Cas9 are being investigated for correcting CAPN3 gene mutations. The goal is to reinstate the production of functional calpain-3 protein. |
| Calcium Dysregulation | Targeting the pathways involved in calcium homeostasis, such as the ryanodine receptor (RYR1) and dihydropyridine receptor (DHPR), may help restore calcium balance and alleviate muscle weakness. Compounds targeting calcium dysregulation are under study as potential therapeutics. |
| Protein Homeostasis | Therapies targeting protein degradation pathways, including the ubiquitin-proteasome system and autophagy, seek to restore protein homeostasis and prevent the buildup of misfolded or damaged proteins. Small molecules that stabilize calpain-3 proteins or facilitate the proper folding of misfolded proteins are under investigation. |
- Types of Calpainopathy Therapy Development
- Gene Therapy
By delivering functional copies of the CAPN3 gene to muscle cells, gene therapy aims to restore the production of functional calpain-3 protein. This approach has the potential to correct the underlying genetic defect and halt disease progression.
- Small Molecule Therapy
Small molecule inhibitors are being investigated to modulate the activity of specific proteins involved in calpainopathy pathogenesis. These inhibitors aim to restore calcium homeostasis, regulate protein degradation pathways, or target downstream molecular pathways associated with muscle degeneration
Our Services
As a frontrunner in the field of biological research and CRO services, our company is dedicated to offering holistic solutions for the diagnostics development and therapy research of calpainopathy. Through collaborations with industry experts, we have established an all-encompassing platform for rare diseases to facilitate calpainopathy therapy development.
Platforms of Calpainopathy Therapy Development
Animal Models of Calpainopathy
Recognizing the significance of dependable animal models in calpainopathy disease research, our company is committed to offering animal model development services that facilitate preclinical research and aid in drug discovery endeavors.
| Genetically Engineered Models | ||
|---|---|---|
Genetic modification plays a crucial role in developing animal models of calpainopathy. Our company has achieved successful establishment of genetically engineered models of calpainopathy through three distinct pathways.
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| Optional Models | CAPN3 Knockout Model CAPN3 Transgenic Model |
CAPN3 Conditional Knockout Model CAPN3 Overexpression Model |
| Optional Species | Mice, Rats, Zebrafish, Canines, Others | |
With complete animal species resources, we can meet your diversified preclinical research including drug safety evaluation and pharmacokinetic analysis. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Lasa-Elgarresta, Jaione, et al. "Calcium mechanisms in limb-girdle muscular dystrophy with CAPN3 mutations." International journal of molecular sciences 20.18 (2019): 4548.
- Angelini, Corrado. "Calpainopathy." (2017).
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.