Omaveloxolone: An activator of Nrf2 for the treatment of Friedreich's ataxia

Profeta, V., McIntyre, K., Wells, M., Park, C., & Lynch, D. R. (2023). Expert opinion on investigational drugs, 10.1080/13543784.2023.2173063. Advance online publication. doi:10.1080/13543784.2023.2173063 

 Although the neurologic phenotype of FRDA is well-defined, there are currently no established pharmacological treatments. Omaveloxolone, a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, is currently under review by the Food and Drug Administration (FDA) and has the potential to be the first approved treatment for FRDA. In the present report, we have reviewed the basic and clinical literature on Nrf2 deficiency in FRDA, and evidence for the benefit of omaveloxolone.

Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets

Konrad Teodor Sawicki, Adam De Jesus and Hossein Ardehali; Circulation Research. 2023;132:379–396, doi:10.1161/CIRCRESAHA.122.321667 

 Iron dysregulation ranges from iron deficiency to iron overload and is seen in many types of cardiovascular disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, and Friedreich’s ataxia. Recently, the use of intravenous iron therapy has been advocated in patients with heart failure and certain criteria for iron deficiency. Here, we provide an overview of systemic and cellular iron homeostasis in the context of cardiovascular physiology, iron deficiency, and iron overload in cardiovascular disease, current therapeutic strategies, and future perspectives.

Deficient mitochondrial respiration impairs sirtuin activity in dorsal root ganglia in Friedreich Ataxia mouse and cell models

Arabela Sanz-Alcazar, Elena Britti, Fabien Delaspre, Marta Medina-Carbonero, Maria Pazos-Gil, Jordi Tamarit, Joaquim ROS, Elisa Cabiscol bioRxiv 2023.02.01.526688; doi:10.1101/2023.02.01.526688

In the present study, we found that in primary cultures of DRG neurons as well as in DRGs from the FXNI151F mouse model, frataxin deficiency resulted in lower activity and levels of the electron transport complexes, mainly complexes I and II. As a consequence, the NAD+/NADH ratio was reduced and SirT3, a mitochondrial NAD+-dependent deacetylase, was impaired. We identified alpha tubulin as the major acetylated protein from DRG homogenates whose levels were increased in FXNI151F mice compared to WT mice.