Guía de Evaluación Diagnóstica y Discapacidad en Pacientes con Ataxias y Paraparesias Espásticas Hereditarias

Francisco Javier Arpa Gutiérrez, María José Abenza Abildúa, Idoia Rouco Axpe. Sociedad Española de Neurología (2022). ISBN: 978-84-124320-4-6 . https://www.edicionessen.es

El objetivo de este trabajo, dirigido a neurólogos en general y a otros facultativos de especialidades médicas como medicina física y rehabilitadora, atención primaria, medicina interna, medicina del trabajo, etc., es facilitar la correcta valoración diagnóstica y de la discapacidad en los pacientes con AH y PEH. Una gradación completa y homogénea de su situación clínica aumentaría la posibilidad de acceder a recursos sociales y legales adecuados a su situación.

The Use of Enhanced Recovery After Surgery Protocols and Sugammadex in a Friedreich Ataxia Patient Who Underwent Robotic Surgery: A Case Report of a Patient Who Required No Postoperative Opioids and Was Discharged Home Earlier Than Anticipated

Lori P. Russo, Daniel Haddad, Daniel Bauman, Mina M. Fam (September 26, 2022). Cureus 14(9): e29590. doi:10.7759/cureus.29590

Anesthesia in general must be carefully planned in FRDA patients to allow for the best possible recovery and minimize complications. Due to the underlying neuromuscular compromise seen in these patients, their ability to recover from the pharmacologic and physiologic changes associated with anesthesia can be more difficult. They are prone to sensitivity to opioids, sedatives, and neuromuscular blocking agents (NMBAs) and are less likely to tolerate hemodynamic changes. Our review revealed no literature to suggest the routine use of Enhanced Recovery After Surgery (ERAS) protocols in FRDA patients or in patients with neuromuscular disease in general. The use of sugammadex has also been shown to be safe, and literature suggests superiority in both the general population and those with neuromuscular conditions. Our understanding is that there is very limited literature in regard to the safe use of sugammadex in FRDA patients.

The inherited cerebellar ataxias: an update

Coarelli G, Wirth T, Tranchant C, Koenig M, Durr A, Anheim M.; J Neurol. 2022 Sep 24. doi: 10.1007/s00415-022-11383-6. 

We describe new therapeutic leads: antisense oligonucleotides approach in polyglutamine SCAs and viral gene therapy in Friedreich ataxia. This review provides support for diagnosis, genetic counseling and therapeutic management of ICAs in clinical practice.

Diagnostic Delay and Clinical Features in Friedreich’s Ataxia

Mehmet Fatih Yetkin, Murat Gültekin, Merve Akcakoyunlu, Recep Baydemir, Ayse Çağlar Sarılar, Mehmet Canpolat, Hüseyin Per; Turk Noroloji Dergisi, cilt.28, sa.2, ss.97-101, 2022 (Hakemli Dergi). DOI:10.4274/tnd.2022.26780

Conclusion: This study is the first study to evaluate the diagnosis delay in patients with FRDA in our country. Although FRDA was the most common hereditary ataxia, in our study, it was shown that there was a significant delay in diagnosis in patients with FRDA. There is a need for studies that will raise awareness of public and health professionals about FRDA.

FRIEDREICH'S ATAXIA AND ITS CARDIOVASCULAR MANIFESTATIONS

Bryam Esteban Coello Garcia, Karina Noemi Contreras Garcia, Priscila Jazmin Sarango Lapo, Tatiana Carolina Espinoza Coyago, Johanna Belen Illescas Aguilera, Bonny Maria Montalvan Nivicela, Karen Sofia Suscal Pelaez; EPRA International Journal of Multidisciplinary Research (IJMR) -Volume: 8, Issue: 9, September 2022, DOI:10.36713/epra11261 

 The aim of this bibliographic review is to inform the scientific community of the presence of systemic manifestations, especially cardiovascular, in Friedreich's Ataxia; since this disease is not only characterized by the presence of neurological alterations, but also of affections to different apparatuses and systems of the human body, such as the heart, due to the cellular alteration that Friedreich's Ataxia causes.

Gene Expression Quantification to Assess Frataxin Replacement Therapies in Friedreich’s Ataxia

M. Baile, D. Schecter, A. Miller, T. Galas, N. Scherer, R. Chen, N. Ruiz, D. Bettoun.; Mov Disord. 2022; 37 (suppl 1). Meeting: 2022 International Congress (September 15-18, 2022. Madrid, Spain) 

 Quantitation of expression levels of a small number of genes in buccal cells can be used to discriminate between healthy individuals and patients with FRDA. Treatment with CTI-1601 is effective in restoring the expression levels of 6 of those genes to levels similar to those observed in healthy individuals.

Tissue Frataxin Increases After Administration of CTI-1601, a Frataxin Replacement Therapy in Development for the Treatment of Friedreich’s Ataxia

D. Bettoun, T. Galas, D. Schecter, N. Ruiz, R. Clayton, J. Farmer.; Mov Disord. 2022; 37 (suppl 1).Meeting: 2022 International Congress (September 15-18, 2022. Madrid, Spain) 

In this first clinical study of CTI-1601, a therapy intended to increase FXN in patients with FRDA, increases in FXN levels were seen in multiple tissues. These observed increases in FXN after 7 days of QD dosing of 50 or 100 mg CTI-160 are potentially clinically relevant since 2- to 3-fold increases in FXN in patients with FRDA may achieve FXN levels observed in asymptomatic heterozygous carriers [1, 2]. CTI-1601 was generally well-tolerated. These data support the continued study of CTI-1601 as a treatment for patients with FRDA.

Activation of a type I interferon response associated with acute frataxin knockdown in iPSC-derived cardiomyocytes

Cotticelli MG, Xia S, Truitt R, Doliba NM, Rozo AV, Tobias JW, Lee T, Chen J, Napierala JS, Napierala M, Yang W, Wilson RB.; Dis Model Mech. 2022 Sep 15:dmm.049497. doi: 10.1242/dmm.049497 

We confirmed that in iPSC-derived cardiomyocytes, loss of frataxin leads to mitochondrial dysfunction. The type I interferon response was activated in multiple cell types following acute frataxin knockdown and was caused, at least in part, by release of mitochondrial DNA into the cytosol, activating the cGAS-STING sensor pathway.

The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy

Ning Guo, Ji-Bin Liu, Wen Li, Yu-Shui Ma, Da Fu; Journal of Advanced Research, Volume 40, 2022, Pages 135-152, doi:10.1016/j.jare.2021.11.018. 

CRISPR/Cas9 also provides a possible therapeutic strategy for Friedreich's ataxia (FRDA). For example, removing the GAA expansions of the frataxin gene (FXN) in vitro and in vivo alleviates related symptoms dramatically but with some unexpected side effects like p53-mediated cell proliferation delay.

A Study to Assess the Safety and Efficacy of Vatiquinone in Participants With Friedreich Ataxia

ClinicalTrials.gov Identifier: NCT05515536

The primary objective of this study is to assess the long-term safety of vatiquinone in participants with Friedreich ataxia (FA) previously exposed to vatiquinone in Study PTC743-NEU-003-FA (NCT04577352) or Study PTC743-NEU-005-FA

Phase 3 

Study Type : Interventional (Clinical Trial) 

Estimated Enrollment : 140 participants 

Allocation: N/A 

Intervention Model: Single Group Assignment 

Masking: None (Open Label) 

Primary Purpose: Treatment 

Official Title: Long-Term Open-Label Study to Assess the Safety and Efficacy of Vatiquinone in Patients With Friedreich Ataxia 

Estimated Study Start Date : November 1, 2022 

Estimated Primary Completion Date : December 31, 2027 

Estimated Study Completion Date : December 31, 2027