Friedreich Ataxia (FRDA)
Friedreich ataxia (FRDA) is a progressive, neurodegenerative disorder that affects approximately 1 in 50,000 individuals. FRDA commonly presents with gait and limb ataxia, dysarthria, areflexia, vibratory and position dysfunction, and muscle weakness. Our company specializes in providing cutting-edge preclinical research services tailored to accelerate the translation of research findings into clinical applications, particularly in the field of FRDA.
Overview of FRDA
Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by mutations in the gene encoding the protein frataxin (FXN). The most common mutation in FRDA is the expansion of the GAA triplet in the first intron of the FXN gene, leading to epigenetic silencing of the gene. This results in a deficiency of frataxin protein, which is crucial for iron metabolism and the biogenesis, maintenance, and repair of Fe-S clusters in mitochondria.
- Pathogenesis of FRDA
The pathogenesis of FRDA involves impairment of Fe-S clusters, mitochondrial dysfunction, and eventual apoptosis, particularly affecting areas like the cerebellum, spinal cord, heart, and pancreas. Additional mutations in the FXN gene or compound heterozygous mutations can further contribute to the disease's manifestation. The genetic cause of FRDA was identified in 1996, highlighting the importance of understanding the pathogenesis for developing targeted therapies for this devastating condition.
Fig.1 Effects of FRDA disease on the organism. (Payne, R. Mark. 2022)Animal Models of FRDA
Knockout models of the frataxin gene have been unsuccessful due to lethality in embryonic development. However, recent advancements in using transgenic mice with human FXN transgene containing GAA triplet expansions have shown promise in reflecting key aspects of FRDA. For instance, the YG8JR model, which lacks murine frataxin and carries human FXN with around 800 repeats, closely mimics the genetic profile of human, making it an ideal model for testing potential therapies.
Therapeutics Development of FRDA
Several therapeutic strategies are being investigated for FRDA, ranging from enhancing energy metabolism and antioxidant therapy to gene therapy. The use of viral vectors, particularly adeno-associated virus (AAV), shows promise in delivering functional FXN to affected cells. Studies have shown that AAV9 and AAVrh10 are effective in transducing neurons and astrocytes in the central nervous system, making them potential candidates for gene therapy in FRDA.
Our Services
With a strong focus on accelerating the translation of research findings into clinical applications, we offer comprehensive FRDA diagnostics and therapy development services. Our experienced team is well-versed in developing various therapeutic modalities for FRDA. Our expertise extends to the cutting-edge realm of adeno-associated virus (AAV) gene therapy, a promising avenue for FRDA therapy development.
Platforms of FRDA Therapy Development
FRDA Animal Model Service: The study of FRDA through animal models plays a crucial role in uncovering the underlying mechanisms of the disease and identifying potential therapeutic targets. We excel in FRDA animal model development services, where we have refined the creation of transgenic mouse models integrating human FXN transgenes with GAA triplet expansions.
If you are interested in our services or require further information, please contact us, and our team will be happy to assist you.
Reference
- Payne, R. Mark. "Cardiovascular Research in Friedreich Ataxia: Unmet Needs and Opportunities." Basic to Translational Science 7.12 (2022): 1267-1283.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.