Longitudinal dentate nuclei iron concentration and atrophy in Friedreich ataxia: IMAGE-FRDA

Phillip Ward, Ian H Harding, Thomas G Close, Louise A Corben, Martin B Delatycki, Elsdon Storey, Nellie Georgiou-Karistianis, Gary F. Egan. bioRxiv 464537; doi: 10.1101/464537 (This article is a preprint and has not been peer-reviewed)

Progressive dentate nuclei pathology is evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a two-year period highlights the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia

Lynch, D. R., Farmer, J. , Hauser, L. , Blair, I. A., Wang, Q. Q., Mesaros, C. , Snyder, N. , Boesch, S. , Chin, M. , Delatycki, M. B., Giunti, P. , Goldsberry, A. , Hoyle, C. , McBride, M. G., Nachbauer, W. , O'Grady, M. , Perlman, S. , Subramony, S. H., Wilmot, G. R., Zesiewicz, T. and Meyer, C. (2018), Ann Clin Transl Neurol. . doi:10.1002/acn3.660

Treatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160 mg/day appears to improve neurological function. Therefore, omaveloxolone treatment is being examined in greater detail at 150 mg/day for Friedreich ataxia.