Therapeutic Prospects for Friedreich's Ataxia

Abstract

Friedreich's ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure.

Keywords: Friedreich’s ataxia; frataxin; gene therapy; mitochondria; oligonucleotide; oxidative stress.

Figure 1.. A 30-year perspective of FRDA research.

Blue bars depict the number of publications appearing in PubMed per year from 1988 – 2017. The data was obtained by entering the search criteria “Friedreich’s ataxia” OR “Friedreich ataxia” OR “frataxin” in PubMed. The black line depicts the dollar amount (in millions) corresponding to grants funded by the National Institutes of Health (NIH) per year from 1988 – 2017 as identified by entering the search terms “Friedreich’s ataxia” OR “Friedreich ataxia” OR “frataxin” in the NIH RePORT search engine. The orange bars show the number of clinical trials initiated per year from 1988 – 2017 as identified on ClinicalTrials.gov using the search term “Friedreich’s ataxia”.

Box 1, Figure I.. Multi-level therapeutic strategies for FRDA.

The flow diagram illustrates many phases underlying disease manifestation in FRDA, highlighting multiple and diverse opportunities for therapeutic intervention (text bubbles). Strategies aimed to increase FXN/frataxin levels are shown in blue, while approaches aimed at improving consequences of frataxin deficiency are shown in orange. The clinical development stage for these strategies can be found on the Friedreich’s Ataxia Research Alliance website.