Centronuclear Myopathy
Centronuclear myopathy is a rare genetic muscle disorder characterized by muscle weakness and wasting that primarily affects skeletal muscles. Our company is a leader in the field of rare diseases, providing researchers with cutting-edge technology, innovative ideas, and personalized therapy development services.
Overview of Centronuclear Myopathy
Centronuclear myopathy also known as myotubular myopathy, is a rare genetic muscle disorder characterized by abnormal positioning of the muscle nuclei within the muscle fibers. This condition primarily affects the skeletal muscles, leading to muscle weakness and impaired muscle function. Centronuclear myopathy is a complex genetic disorder with seven identified pathogenic genes, including BIN1, CCDC78, DNM2, MTM1, RYR1, SPEG, and TTN.
Fig.1 Scheme of MTM1, DNM2, BIN1, and RyR1 protein domains. (Gómez-Oca, R., et al., 2021)Pathogenesis of Centronuclear Myopathy
The pathogenesis of centronuclear myopathy involves defects in muscle membrane trafficking and organization, leading to the abnormal positioning of nuclei within muscle cells. Mutations in genes like MTM1, BIN1, and DNM2 disrupt normal muscle function, causing weakness and atrophy. The gene variants cause disorganization of T-tubules and triads in skeletal muscle suggesting these genes have a common pathway during T-tubule biogenesis.
Fig.2 Schematic illustration of pathogenic alterations in skeletal muscle caused by mutations in MTM1, BIN1, DNM2, and RYR1. (Gómez-Oca, R., et al., 2021) Diagnostics Development of Centronuclear Myopathy
Genetic testing is essential for confirming the diagnosis and identifying the specific genetic mutation causing centronuclear myopathy. It can involve sequencing the MTM1 gene or other genes associated with the condition.
Therapeutics Development of Centronuclear Myopathy
| Therapies | Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Small Molecule Drug Therapy | Edrophonium | NMJ transmission improvement | AChE | Approved |
| Pyridostigmine | NMJ transmission improvement | AChE | Approved | |
| AZD8055 | Autophagy activation | mTOR | Preclinical studies | |
| Antioxidant N-acetylcysteine | Decrease oxidative stress | ROS | Phase I/II trials | |
| Cell Therapy | Cell transplantation | Muscle regeneration | / | Preclinical studies |
| Gene Therapy | AAV-shRNA | Normalization/reduction of DNM2 | DNM2 | Preclinical studies |
| AAV-MTM1 | MTM1 expression | MTM1 | Phase I/II trials | |
| AAV-BIN1 | BIN1 expression | BIN1 | Preclinical studies |
Our Services
We are dedicated to advancing the understanding and therapy of rare diseases through ongoing research and collaboration with leading healthcare institutions. Relying on our animal models and therapeutic development platform, we provide you with all aspects of rare disease diagnostics and therapeutics development.
Therapy Development Platforms
Animal Models of Centronuclear Myopathy
Animal models play a pivotal role in advancing research efforts by allowing scientists to study the underlying mechanisms of the disease, pinpoint potential targets for therapeutic intervention, and assess the safety and efficacy of new therapy modalities. Our company provides a variety of centronuclear myopathy disease animal models to support your related research.
Chemical induction models of centronuclear myopathy involve inducing the disease phenotype in animal models through the administration of specific chemicals or compounds.
Optional Models: Bupivacaine-induced model, etc.
Utilizing transgenic or gene editing techniques such as CRISPR/Cas9 to induce mutations in genes like DNM2 and MTM1 can help replicate the centronuclear myopathy disease phenotype in animal models.
Optional Models: Mtm1tm1.1Jman model; Dnm2tm1.1Ics model, etc.
Why Choose Us
Our company, with expertise in rare diseases, offers tailored solutions, including pharmacokinetics analysis and drug safety evaluation, to support researchers in the study and therapeutic development for centronuclear myopathy.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Fujise, Kenshiro et al. "Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants." International journal of molecular sciences 23.11 (2022): 6274.
- Gineste, Charlotte, and Jocelyn Laporte. "Therapeutic approaches in different congenital myopathies." Current opinion in pharmacology 68 (2023): 102328.
- Gómez-Oca, Raquel et al. "Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances." International journal of molecular sciences 22.21 (2021): 11377.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.