Calpainopathy
Preclinical drug screening is one of the key initial steps in the development of new therapies for rare diseases such as limb-girdle muscular dystrophy type 2A (LGMD2A). Our company is committed to developing a variety of animal models to help our clients study the pathophysiology of this disease and develop effective therapeutic approaches. To date, we have established several mouse and zebrafish models to test and find promising drug candidates that may improve LGMD2A/R1 disease symptoms. Our expertise in genetics and molecular biology, combined with its state-of-the-art facilities and equipment, makes us a valuable partner for researchers and clinicians working in this field.
Background
Calpainopathy is a group of genetic disorders that affect the function of calpain enzymes, which play a crucial role in muscle development and maintenance. LGMD2A is one of the most common calpainopathy forms, characterized by progressive muscle weakness and wasting. Patients with LGMD2A have normal levels of dystrophin and sarcoglycan, however, calpain 3 (CAPN3) levels are not detected in the muscles. The development of effective therapies for calpainopathies has been challenging due to the complex genetic and cellular mechanisms involved.
Animal models have played a crucial role in the development of new therapies for calpainopathy, including the use of the LGMD2A/R1 mice model to test potential therapeutic targets. The genetic heterogeneity of calpainopathy has made identifying effective therapies challenging. However, the use of animal models has provided valuable insight into the underlying mechanisms of the disease.
Fig. 1 Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a LGMD2A/R1 mouse model. (Sahenk Z, et al., 2021)
Our Services
Animal models may not fully capture the range and severity of symptoms seen in humans with calpainopathies, which may limit the translatability of findings to human. However, the availability of these models has provided valuable insights into the pathophysiology of calpainopathies and facilitated the development of multiple therapies, such as plasmid-mediated gene therapy. We are committed to customizing animal models through precise genome editing techniques to improve translation chances.
- New LGMD2A/R1 mice
We help our clients generate four LGMD2A/R1 mouse models, all of which are null for CAPN3. We produce mouse models by utilizing the widely used inbred strains: 129/Sv, DBA2/J, and FVB/NJ or generate knockouts in strains from CC041/UncJ to obtain mouse models. These mice can be used as a tool to help the research community better understand LGMD2A and its therapeutic approach. - CAPN3b-deficient zebrafish
Using mice for drug testing is challenging because mouse models do not show muscle symptoms until old age and reproduce slowly. We offer our clients several unique zebrafish lines that disrupt CAPN3 as animal models to test and screen new drug candidates.
Our animal models can be used for the evaluation of a variety of preclinical-stage therapies, including several gene therapies, cellular therapies, and drug therapies, such as glucocorticoid therapy, AAV-mediated therapies, CRISPR-Cas9, MYO-029, and AMBMP.
As a leading company in biotechnology, our company is committed to developing innovative solutions for the diagnosis and therapy of genetic disorders such as calpainopathy. By leveraging the latest advances in animal models, we are well-positioned to contribute to the development of effective therapies for calpainopathy and other genetic disorders. If you are interested in our animal modeling services, please contact us for more information.
Reference
- Sahenk, Z.; et al. Systemic delivery of AAVrh74. tMCK. hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1. Molecular Therapy-Methods & Clinical Development, 2021, 22: 401-414.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
