Corpus ID: 56881041

Investigating novel therapies for Friedreich’s ataxia

  title={Investigating novel therapies for Friedreich’s ataxia},
  author={M. Sherzai},
Friedreich’s ataxia (FRDA) is a progressive neurodegenerative disorder caused by a homozygous GAA repeat expansion mutation in intron 1 of the frataxin gene (FXN), which instigates transcriptional issues. As a consequence, reduced levels of frataxin protein lead to mitochondrial iron accumulation, oxidative stress and ultimately cell death; particularly in dorsal root ganglia (DRG) sensory neurons and the dentate nucleus of the cerebellum. In addition to neurological disability, FRDA is… Expand
HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich’s Ataxia
It is shown that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks, but no increase in frataxin protein levels was observed. Expand
New developments in pharmacotherapy for Friedreich ataxia
In this review article, the authors discuss the current and prior in vivo and in vitro research studies related to the treatment of FRDA, with a particular interest in future implications of each therapy. Expand


Translating HDAC inhibitors in Friedreich’s ataxia
The evidence that histone postsynthetic modifications and heterochromatin formation are responsible for FXN gene silencing in FRDA is reviewed, along with efforts to reverse silencing with drugs that target histone modifying enzymes. Expand
Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy
The present paper will initially focus on the epigenetic changes seen in FRDA patients and their role in the silencing of FXN gene and will be concluded by considering the potential epigenetic therapies. Expand
Friedreich's ataxia: from disease mechanisms to therapeutic interventions.
Pilot studies have shown the potential effect of antioxidant therapy in this condition and provide a strong rationale for designing larger clinical randomized trials. Expand
Small molecules affecting transcription in Friedreich ataxia.
A number of laboratories have focused on small molecule activators of FXN gene expression as potential therapeutics, and this review summarizes the current status of these efforts, as well as the molecular basis for gene silencing in FRDA. Expand
Pathophysiogical and therapeutic progress in Friedreich ataxia.
A promising therapeutic strategy that is currently the subject of intense research is to directly target the heterochromatin state of the GAA repeat expansion with histone deacytelase inhibitors (HDACi) to restore frataxin levels. Expand
HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model
Lack of acute toxicity, normalization of frataxin levels and of the transcription profile changes resulting from fratxin deficiency provide strong support to a possible efficacy of this or related compounds in reverting the pathological process in Friedreich ataxia, a so far incurable neurodegenerative disease. Expand
Cell and gene therapy for Friedreich ataxia: progress to date.
Since individuals with FRDA produce frataxin at low levels, increased expression should not elicit an immune response, and hence any increase in protein level is expected to be therapeutically beneficial. Expand
Friedreich ataxia: molecular mechanisms, redox considerations, and therapeutic opportunities.
The molecular mechanisms that underlie the disease phenotypes and the different hypothesis about the function of frataxin are highlighted and the most recent therapeutic approaches for this severe disease that actually has no efficient treatment are presented. Expand
Therapeutic approaches for the treatment of Friedreich’s ataxia
Gene therapy, a field which has undergone significant advances in recent years, may offer a promising treatment for FRDA in the future and a collection of approaches provides many possible opportunities for treating this multisystem disorder. Expand
Therapeutic Developments in Friedreich Ataxia
Several major therapeutic initiatives aimed at increasing frataxin expression, reversing mitochondrial iron accumulation, and alleviating oxidative stress are in preclinical and clinical development and are reviewed herein. Expand