Calpainopathy
Calpainopathy is a condition defined by muscular wasting and weakness. Our company does take pride in having a sector of professionals and scientists who specialize in the research of calpainopathy, which forms the basis for the creation of advanced diagnostic and therapeutic agents. As your dependable partner, we provide a full range of services designed to meet the needs of your scientific research.
Introduction to Calpainopathy
Calpainopathy, or autosomal recessive limb-girdle muscular dystrophy (LGMD), is a disorder that results from an inheritance pattern of the hip girdle and shoulder girdle muscles. Subtypes of calpainopathy include pelvic-femoral LGMD, scapulohumeral LGMD, and HyperCKemia, among others. Calpainopathy is known to be infrequent, occurring in only 1 in 80,000 people.
Fig. 1 Illustration of the pathological features of CAPN3 deficiency in the skeletal muscle. (Lasa-Elgarresta, et al., 2019)Pathogenesis of Calpainopathy
The calpainopathy pathogenesis is framed around the mutations within the CAPN3 gene, which is responsible for encoding the important protein known as calpain-3.
Calpain-3 Protein
Foremost in skeletal muscles, calpain-3 functions primarily as a protease and a structural protein. During muscle remodeling, calpain-3 contributes through the cleavage of sarcomeres and cytoskeletal proteins while also regulating Ca2+. Moreover, as a stabilizer of the triad protein complex, calpain-3 helps modulate excitations and contractions of the muscles and stabilizes the complex protein which regulates the Ca2+.
CAPN3 Gene
The CAPN3 gene harbors mutations that alter the normal functioning of calpain-3, resulting in its inability to effectively manage muscle protein metabolism and preservation. At the same time, calcium channels like ryanodine receptor (RYR1) and dihydropyridine receptor (DHPR) are also damaged. Calcium mismanagement leads to muscle tissue atrophy and degeneration, hence causing calpainopathy.
Diagnostics Development of Calpainopathy
To improve the prognosis of calpainopathy, a comprehensive treatment strategy requires prompt and precise diagnosis. These steps outline the primary methodologies for diagnosis:
- 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
Effective gene therapy is aimed at the muscle cells responsible for the production of a calpain-3 protein with normal activity. This strategy can potentially fix the genetic defect responsible for the disease and stop its advancement.
- Small Molecule Therapy
Currently, small molecular inhibitors are being looked at that could modify some proteins relevant to the pathogenesis of calpainopathy. Such inhibitors are designed to restore calcium balance, modulate protein degradation pathways, or act on muscle disease associated molecular pathways.
Our Services
Our company is engaged in biological research services, hence, our ability to provide niche solutions for diagnostics development and therapy research makes us a leader in calpainopathy. Its therapeutic development is greatly impeded so we have partnered with industry leaders to build a multi-purpose platform for rare diseases that will allow rapid development of calpainopathy therapeutics.
Platforms of Calpainopathy Therapy Development
Animal Models of Calpainopathy
Understanding the importance of appropriately chosen animal models in calpainopathy disease research, our company undertakes to make available animal model development which support preclinical research and contribute to drug discovery.
| 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 | |
Armed with complete animal species resources, we are ready to serve your extensive 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.