DNA REPAIR PATHWAYS ARE ALTERED IN NEURAL CELL MODELS OF FRATAXIN DEFICIENCY

Jara Moreno-Lorite, Sara Pérez-Luz, Yurika Katsu-Jiménez, Daniel Oberdoerfer, Javier Díaz-Nido, Molecular and Cellular Neuroscience, 2021, 103587, doi:10.1016/j.mcn.2020.103587. 

 These results suggest that the deficiency of FXN leads to a down-regulation of DNA repair pathways that synergizes with oxidative stress to provoke DNA damage, which may be involved in the pathogenesis of FRDA. Thus, a failure in DNA repair may be considered a shared common molecular mechanism contributing to neurodegeneration in a number of hereditary ataxias including FRDA.

Friedreich ataxia in COVID-19 time: current impact and future possibilities

Tommaso Schirinzi, Andrea Sancesario, Enrico Castelli, Enrico Bertini & Gessica Vasco; Cerebellum & Ataxias volume 8, Article number: 4 (2021). doi:10.1186/s40673-020-00127-9

COVID-19 outbreak profoundly impacted on daily-life of patients with neurodegenerative diseases, including those with ataxia. Effects on interventional trials have been recently described. Conversely, changes in physical activity programs, which are crucial in care of ataxic patients, have not been assessed yet. Here we used a structured electronic survey to interview twenty patients with Friedreich ataxia (FA) on changes in physical activity during the lockdown in Italy. Regular physiotherapy was interrupted for most patients and up to 60% of them referred a substantial worsening of self-perceived global health. However, FA patients (especially those mildly affected) adopted voluntarily home-based training strategies and, in 30% of cases, used technology-based tools (TBTs) for exercise. COVID-19 crisis thus disclosed the urgent need to support ataxic patients improving systems for remote physical activity and technology-based assistance.

Current report, slide presentation, Form 8-K Exicure, Inc.

Form 8-K Exicure, Inc. Current report, items 7.01 and 9.01; Published: 2021-01-07 On January 7, 2021, Exicure, Inc. (the “Company”) will host a virtual R&D Day on Thursday, January 7, 2021 from 9:00 am to 10:30 am ET to discuss its neuroscience pipeline, including its lead program for Friedreich’s Ataxia (FA). The R&D Day webcast will include a slide presentation, which is attached as Exhibit 99.1 to this Current Report on Form 8-K and incorporated by reference in this Item 7.01. The R&D Day webcast will be available on the Company’s website for 30 days following the event.

LEXEO Therapeutics Launches with $85 Million Series A Financing to Develop Gene Therapies for Rare and Non-Rare Monogenic Diseases

NEW YORK, Jan. 07, 2021 (GLOBE NEWSWIRE) -- LEXEO Therapeutics, a clinical-stage gene therapy company, debuted today with an oversubscribed $85 million Series A financing, led by Longitude Capital and Omega Funds, and joined by Lundbeckfonden Ventures, PBM Capital, Janus Henderson Investors, Invus, Woodline Partners LP, the Alzheimer’s Drug Discovery Foundationi and Alexandria Venture Investments. Proceeds from the financing will help advance the company’s three lead investigational programs, including: LX2006, an IV-administered therapy for cardiomyopathy associated with Friedreich’s ataxia (Phase 1 start planned for 2021); LX1004, a CNS-administered therapy for CLN2 Batten disease (Phase 1/2 completed); and LX1001, a CNS-administered therapy for APOE4-associated Alzheimer’s disease (Phase 1 ongoing).

Developing an Instrumented Measure of Upper Limb Function in Friedreich Ataxia

Louise A. Corben, Khoa D. Nguyen, Pubudu N. Pathirana, Malcolm K. Horne, David J. Szmulewicz, Melissa Roberts & Martin B. Delatycki; Cerebellum (2021). doi:10.1007/s12311-020-01228-1

We have developed an objective measure, the Ataxia Instrumented Measure–Spoon (AIM-S), which consists of a spoon equipped with a BioKin wireless motion capture device, and algorithms that analyse these signals, to measure ataxia of the upper limb during the pre-oral phase of eating. The aim of this study was to evaluate the AIM-S as a sensitive and functionally relevant clinical outcome for use in clinical trials.

Two ways to control CjCas9 expression in the deletion of pathogenic GAA repeat in frataxin gene

Pouiré Yaméogo; Genetic Engineering Research, Vol.9 Iss.3:sc165

Our results showed that despite the self-destruction of the CjCas9 gene, an effective genome editing of the FXN gene was obtained in vitro. CRISPR-SCReT (Stop Codon Read Through), we inserted a stop codon (TGA) at the beginning of the CjCas9 gene to repress its expression. Subsequently, we induced the expression of Cas9 by molecules capable to allow translation despite the presence of the premature stop codon.

Antisense Transcription across Nucleotide Repeat Expansions in Neurodegenerative and Neuromuscular Diseases: Progress and Mysteries

Castro AF, Loureiro JR, Bessa J, Silveira I. Genes. 2020 Nov;11(12). DOI: 10.3390/genes11121418.

Efficacy and Tolerability of Interferon Gamma in Treatment of Friedreich's Ataxia: Retrospective Study

Mehmet Fatih YETKİN and Murat GÜLTEKİN; Noro Psikiyatr Ars. 2020 Sep 21;57(4):270-273. doi: 10.29399/npa.25047. eCollection 2020 Dec. 

 Interferon-gamma (IFN-γ) has been shown to induce frataxin production in many cell types. In this study, the clinical features, tolerability, and the prognosis of individuals with FRDA to whom IFN-γ was administered in a university hospital were evaluated retrospectively and the results were discussed. To the best of our knowledge, this is the first study conducted in our country to evaluate the effect of IFN gamma on this patient group.

FDA requests new trial for Reata's Friedreich's ataxia program; J&J's Tremfya picks up expanded label in Europe

Endpoints News, November 25, 2020. Three months after Reata Pharmaceuticals suggested its Friedreich’s ataxia program omaveloxolone could be delayed, the company revealed that is indeed going to be the case. 

The FDA did not rule out reconsidering omaveloxolone’s application once the new study has been completed, Reata noted.

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.