Limb-Girdle Muscular Dystrophy (LGMD)
Limb-girdle muscular dystrophy (LGMD) is an umbrella term that represents several rare types of muscular dystrophy, which is a chronic (lifelong) condition that affects people of all ages. At the forefront of rare disease research and innovation, our company is dedicated to providing a holistic service for LGMD-related studies and therapeutic development.
Overview of LGMD
With an estimated incidence rate ranging from 1 to 6 individuals per 100,000, LGMD is characterized by progressive muscle weakness and wasting primarily affecting the muscles of the hips and shoulders (limb-girdle region). There are several subtypes of LGMD, each caused by different gene mutations, leading to variations in the age of onset, severity, and progression of symptoms.
Fig.1 Immunohistochemical analysis of sarcomeric and sarcolemmal structures of the individuals with confirmed LGMD-R. (Lorenzoni, P. J., et al., 2023)Pathogenesis of LGMD
LGMD is primarily caused by genetic mutations that affect the structure or function of proteins involved in maintaining the integrity and stability of muscle fibers. These mutations disrupt the normal signaling pathways, leading to muscle fiber degeneration and weakness over time. Depending on the specific subtype, the mutations can affect different proteins, such as sarcoglycans, dysferlin, calpain, and others.
Fig.2 The pathological features of LGMDR1. (Lasa-Elgarresta, J., et al., 2019)Diagnostics Development of LGMD
Genetic testing is essential for the identification of specific gene mutations leading to LGMD subtypes and the development of targeted therapies. LGMD is caused by more than 29 individual genes, corresponding to different subtypes and symptoms.
- CAPN3
- FKRP
- HMGCR
- DYSF
- SGCB
- SGCD
- DES
- GMPPB
- TCAP
- LAMA2
- TRIM32
- Others
Therapeutics Development of LGMD
Small Molecule Drug Therapy
Corticosteroids (such as prednisone and deflazacort) may be prescribed to help slow down the progression of muscle weakness in certain LGMD subtypes. Other drugs, such as immunosuppressants or anti-inflammatory drugs, may be used to manage inflammation or immune-mediated processes.
Gene Therapy
Antisense oligonucleotide (ASO)-mediated exon skipping or Adeno-associated virus (AAV) vector-mediated gene therapy can deliver functional copies of the mutated or missing gene to the affected cells, aiming to restore the production of the essential protein and improve muscle function.
Our Services
As a leader in the rare diseases industry, our company has state-of-the-art animal models and therapeutic development platforms, which position us as a trusted leader in providing innovative solutions for rare diseases such as LGMD.
Platforms of LGMD Therapy Development
Animal Models of LGMD
Animal models play a crucial role in understanding the pathogenesis of LGMD and developing potential therapies. Our company provides you with various animal models of LGMD, which can provide valuable insights into the disease mechanisms, allow researchers to study the effects of potential therapies, and facilitate the development of therapy strategies for LGMD.
Chemical-induced animal models of LGMD involve the administration of specific chemicals or toxins to animals, resulting in muscle damage and phenotypic characteristics resembling certain aspects of LGMD.
Optional Models: Notexin-induced model; Bupivacaine-induced model, etc.
These models involve introducing specific genetic mutations associated with LGMD (such as dysferlin and sarcoglycan, etc.) into the genomes of animals to mimic the disease phenotype.
Optional Models: Dysfprmd model; Sgcdtm1Mcn model; Fkrptm1Itl model, etc.
Why Choose Us
Our deep understanding of the unique needs of researchers allows us to tailor our services to meet your specific requirements. We have cutting-edge technology and resources to support your research including pharmacokinetics analysis and drug safety evaluation.
If you are interested in our services, please feel free to contact us for more details and quotation information of 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.
- Lorenzoni, Paulo Jose et al. "Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review." Arquivos de neuro-psiquiatria 81.10 (2023): 922-933.
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