PTC Therapeutics announced the initiation of its third study of 2020 investigating vatiquinone.

NeurologyLive, December 24, 2020

PTC Therapeutics has announced the initiation of the global phase 3 MOVE-FA study (NCT04577352) of vatiquinone (PTC743) for Friedreich’s ataxia (FA). The study is currently recruiting children and young adults.Initiation of the trial was delayed by COVID-19

The double-blind MOVE-FA trial will evaluate vatiquinone versus placebo in approximately 110 children and young adults with FA in parallel arms over 18 months. Patients will be enrolled from the US, EU, Australia, and Latin America.

A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia (MOVE-FA)

ClinicalTrials.gov Identifier: NCT04577352; December 19, 2020 

Sponsors and Collaborators PTC Therapeutics 

Double-blind, placebo-controlled phase, participants will be stratified by baseline mFARS score (<40 age="" and="" at="" disease="" of="" onset="" or="" screening="" versus="" years="">21 years) and randomized to receive either vatiquinone or placebo using interactive web response system (IWRS). Following completion of the randomized, double-blind, placebo-controlled phase (72 weeks), participants will enter into an open-label extension phase (24 weeks) during which they will receive open-label treatment with vatiquinone at the dose they received in the randomized phase of the study (for participants entering the extension phase who initially received placebo, the dose of vatiquinone will be determined based on age and weight) and then a safety follow-up (10-30 days after last dose).

Insights Into the Roles of the Sideroflexins / SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis

Tifoun, N.; De las Heras, J.M.; Guillaume, A.; Bouleau, S.; Mignotte, B.; Le Floch, N.; Preprints 2020, 2020120583 doi: 10.20944/preprints202012.0583.v1. 

Frataxin (FXN) is a mitochondrial chaperone that interacts with aconitase in a citrate389 dependent manner to convert (3Fe-4S)1+ inactive enzyme into [4Fe-4S]2+ active one within the Krebs cycle. It also interacts with the ISCU-NFS1 (Iron-Sulfur Cluster Scaffold-Cysteine desulfurase) in the final steps of Fe-S formation [81,82]. The reduction of mitochondrial aconitase (ACO2) in SFXN4 KO cells suggests that SFXN4 could participate in the Fe-S biosynthesis maybe through an interaction with Frataxin (FXN). IIt has been previously reported that FECH, an important enzyme for heme biosynthesis, Mfrn1, an iron transporter into the mitochondria, and ABCB10, a protoporphyrin IX transporter, could form a complex in mouse erythroleukemia (MEL) cells to direct iron incorporation into protoporphyrin to form heme . Taken together, those results open the possibility that SFXN4 and FXN interact with other proteins such as aconitase or the ISCU-NFS1 multimeric complex to maturate the Fe-S clusters. We have recently performed a screen with the aim to identify the direct partners of SFXN1 protein in MCF7 cells (Tifoun et al., in preparation) and, even though Sfxn1 does not interact directly with FXN, it is still possible that Sfxn4 could do so. In Sfxn4 mutants Fe-S synthesis is reduced, pointing out that Sfxn4 may play a role in the first steps of Fe-S cluster formation, maybe through FXN interaction. A recent study shows that the ISC (Iron Sulfur Cluster, composed by NFS1, ISCU and FXN) function requires L-Cysteine to generate de disulfide groups necessary to form the Fe-S clusters.