Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model

Tommaso Vannocci, Roberto Notario Manzano, Ombretta Beccalli, Barbara Bettegazzi, Fabio Grohovaz, Gianfelice Cinque, Antonio de Riso, Luca Quaroni, Franca Codazzi, Annalisa Pastore
Disease Models & Mechanisms 2018 : dmm.032706 doi: 10.1242/dmm.032706 Published 24 May 2018

We prove that overexpression of the frataxin gene affects the cellular metabolism. It also lead to a significant increase of oxidative stress and labile iron pool levels. These cellular alterations are similar to those observed when the gene is partially silenced, as it occurs in Friedreich's ataxia's patients. Our data suggest that the levels of frataxin must be tightly regulated and fine-tuned, any imbalance leading to oxidative stress and toxicity.
Viral approaches (AAV), take advantage of a human exogenous FXN gene under the control of strong promoters that induce overexpression of the therapeutic genes. Although the mouse models showed great improvements, the lack of a tight control on the levels of expression could generate the effects detailed in this work with unknown long-term consequences for patients treated this way. Recent studies have taken advantage of the novel CRISPR gene editing approach to produce the desired gene correction as an alternative, gene correction of the endogenous FXN gene by reduction of the GAA expansion seems to be preferable. This strategy has the advantage that frataxin levels would be restored to physiological levels. It is however essential for these studies to determine the effects of different levels of frataxin.

Rehabilitation robots for the treatment of sensorimotor deficits: a neurophysiological perspective

Roger Gassert and Volker Dietz; Journal of NeuroEngineering and Rehabilitation 2018 15:46 doi:10.1186/s12984-018-0383-x

Future rehabilitation approaches will not only profit from the inclusion of robots, but also from an advanced understanding of neurophysiological mechanisms underlying normal and impaired sensorimotor functions, enabled by the use of robots as scientific tools. Resulting insights will benefit the development of advanced rehabilitation robots, and further promote collaboration between engineers, therapists and clinical neurophysiologists.

Oligonucleotides Hold Promise as a Therapy for Friedreich's Ataxia: Friedreich's ataxia currently is incurable, but synthetic antisense oligonucleotides have demonstrated promising results in increasing frataxin gene expression and restoring it to normal levels

AJMG. Volume176, Issue6 June 2018 Pages 1282-1282 doi:10.1002/ajmg.a.38850

Another important point that was demonstrated in this and previous papers is that oligonucleotides increase the expression of FXN. According to Dr. Corey, “That corrects a fundamental defect in the disease specifically at the gene level, so it is a plausible compound for moving forward.”

However, right now the compounds are in the earliest stages, and more evidence is needed that the treatment is safe and effective. “We need to find animal models to begin testing it, and a company needs to be encouraged to develop it,” Dr. Corey says.