Home Based Tele-exercise for People With Chronic Neurological Impairments: COVID and Beyond (Telex)

ClinicalTrials.gov Identifier: NCT04564495. To assess the impact of a 12-week virtual seated physical intervention on cardiovascular health and wellness in people with chronic neurological impairments (CNI). Locations: United States, New York, Burke Neurological Institute, September 25, 2020

Extra-mitochondrial mouse frataxin and its implications for mouse models of Friedreich’s ataxia

Liwei Weng, Laurent Laboureur, Qingqing Wang, Lili Guo, Peining Xu, Leah Gottlieb, David R. Lynch, Clementina Mesaros & Ian A. Blair; Sci Rep 10, 15788 (2020). doi:10.1038/s41598-020-72884-w 

Mature mouse frataxin (78-207) only contributes 7–15% to the total frataxin protein present in mouse tissues. We have also found that truncated mature frataxin (79-207) is present primarily in the cytosol of mouse liver; whereas, frataxin (78-207) is primarily present in the mitochondria. These findings, which provide support for the role of extra-mitochondrial frataxin in the etiology of Friedreich’s ataxia, also have important implications for studies of mitochondrial dysfunction conducted in mouse models of frataxin deficiency.

Apart from our own studies on frataxin isoform E, several other studies have suggested that human mature frataxin can have an extra-mitochondria location. Alternatively, processing of the mature mouse frataxin could proceed in a different manner than in humans. If this is the case, we would suggest that mouse models do not serve as a good model for humans. Finally, as human gene therapy is tested in mouse models, it is possible that the mature human protein will undergo truncations in the mouse tissues, although they will most likely be at different sites because of the differences in amino acid sequence at the amino-terminus compared to mouse frataxin. This will impact on the assessment of efficacy and safety of the human transgene constructs (such as CAG-hFXN-HA) in mouse models.