Friedreich’s Ataxia (FRDA)
Friedreich's ataxia (FRDA) is an inherited neuromuscular disorder. Cardiac complications are the primary drivers of early mortality in FRDA. FRDA cardiomyopathy is a complex and progressive illness with no cure to slow disease progression. Protheragen is a dedicated research service provider focused on rare cardiovascular disorders such as FRDA. We pride ourselves on being a one-stop platform for comprehensive drug discovery and development solutions, integrating rigorous scientific research with broad-ranging experience.
Overview of Friedreich's Ataxia (FRDA)
Friedreich's ataxia (FRDA) is a genetic disorder marked by an autosomal recessive inheritance pattern. Its frequency sits at approximately 1 in 50,000 people, with life expectancy averaging around 38 years. This disorder results in a lack of frataxin, mainly affecting the muscles, the nerves, and the cardiovascular system. Moreover, cardiomyopathy is found in two-thirds of FRDA cases and continues to be the most common cause of death in FRDA individuals.
Fig.1 Manifestations of FRDA. (Payne R. M., 2022)Pathogenesis of Friedreich's Ataxia (FRDA)
Friedreich's ataxia (FRDA) is a genetic disease typically linked to a GAA repeat expansion in the first intron of the FXN gene, which is responsible for frataxin. The protein frataxin is involved with the synthesis of iron-sulfur clusters. These clusters are essential for the proper functioning of the electron transport chain, and, regulating heme and iron homeostasis, suggesting that commonly reduced levels of frataxin in FRDA would damage mitochondria and cause dysfunction while leading to the excessive accumulation of iron which would increase oxidative stress and cell death in the nervous and cardiovascular systems.
Fig.2 Histological images of FRDA individuals. (Lees, J. G., et al., 2022)Therapeutics Development for Friedreich's Ataxia (FRDA)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| ASP2016 | Revive normal cellular activities by restoring functional expression of FXN and increasing frataxin protein levels. | FXN | NCT06483802 | Phase I |
| AAVrh.10hFXN | Use adeno-associated viral vector serotype rh10 to transfect a functional copy of the FXN gene in individual cells. | FXN | NCT05302271 | Phase I |
| Nicotinamide | Alter gene expression by inhibiting HDACs and increasing NAD+ concentration in the cells. | PARP1 | NCT03761511 | Phase II |
| Epoetin alfa | Reduction of oxidative stress and enhancement of mitochondrial activity can ease the cellular dysfunctions associated with FRDA. | EPO receptor | NCT01493973 | Phase II |
| Resveratrol | Altering the processes of cellular energy metabolism and mitochondria activities. | NLRP3, SIRT1 | NCT03933163 | Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
The full range of services our company offers encompasses every phase of the drug development process. From the initial diagnostic and therapeutic development to the complex refinement modeling of diseases, we ensure that all levels of research have unrivaled rigor. Moreover, our advanced preclinical pharmacokinetic and drug safety evaluation capabilities increase the speed at which we transition from bench to bedside while still ensuring compliance and quality.
Therapeutic Development Services
Animal Model Development for FRDA
Creating animal models for FRDA is important for the disease understanding and possible therapy evaluation. Using sophisticated molecular techniques, our company offers tailored FRDA animal model development services aimed at serving the specific FRDA research goals of our clients.
Genetically Engineered Animal Model
Animal models are created by inducing mutations in the FXN gene, to mimic the disease's neurodegenerative and cardiomyopathic features for research and therapeutic exploration.
Optional models:
- Fxn conditional knockout model
- MCK-Fxnflox/flox model
- YAC Fxn transgenic model
- Other models
When you partner with Protheragen, you acquire a collaborative associate dedicated to providing innovative, detailed research solutions that streamline and reduce risk in the drug development process for uncommon cardiovascular disorders. For any questions, feel free to contact us.
References
- Payne, R Mark. "Cardiovascular Research in Friedreich Ataxia: Unmet Needs and Opportunities." JACC. Basic to translational science 7.12 (2022): 1267-1283.
- Lees, Jarmon G et al. "Cellular pathophysiology of Friedreich's ataxia cardiomyopathy." International journal of cardiology 346 (2022): 71-78.
For research use only, not for clinical use.