Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia

Atteneri Hernández-Torres, Fernando Montón, Stephany Hess Medler, Érika de Nóbrega and Antonieta Nieto; Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia. DOI:10.1017/S1355617720000958 Published online by Cambridge University Press: 14 October 2020

At follow-up, cerebellar symptoms had worsened, and patients presented greater disability. Differences between baseline and follow-up were observed in motor and cognitive reaction times, several trials of the Stroop test, semantic fluency, and block designs. No other cognitive changes were observed. Deterioration in simple cognitive reactions times and block designs performance correlated with the progression of cerebellar symptoms. Our study has demonstrated for the first time that patients with FRDA experience a significant decline over time in several cognitive domains. Specifically, after an eight-year period, FRDA patients worsened in processing speed, fluency, and visuoconstructive skills. This progression is unlikely to be due to greater motor or speech impairment.

Larimar Therapeutics Announces Formation of Scientific Advisory Board

BALA CYNWYD, Pa., Oct. 13, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced the formation of its Scientific Advisory Board (SAB). Larimar’s SAB is comprised of distinguished research scientists, professors and industry experts recognized as key opinion leaders in the fields of rare disease, pediatrics and mitochondrial disease. “Larimar is privileged to have this group of prestigious, multidisciplinary advisors who are committed to advancing the research and development of CTI-1601 for Friedreich’s ataxia,”

Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells

Vilema-Enríquez G, Quinlan R, Kilfeather P, Mazzone R, Saqlain S, Del Molino Del Barrio I, Donato A, Corda G, Li F, Vedadi M, Németh AH, Brennan PE, Wade-Martins R.; J Biol Chem. 2020 Oct 7:jbc.RA120.015533. doi: 10.1074/jbc.RA120.015533

Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target.

Sexual function, intimate relationships and Friedreich ataxia

Louise A. Corben, Mireille M. Hermans, Alice Marks, Louise M. Crowe & Martin B. Delatycki; J Neurol (2020). https://doi.org/10.1007/s00415-020-10258-y 

 This study confirmed FRDA impacts sexual functioning, sexual satisfaction and the capacity to form intimate relationships. Understanding the nature and extent of SD is critical to developing interventions and recommendations designed to enhance sexual function, sexuality, and intimate relationships for individuals with FRDA.

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich’s Ataxia

Marinela Vavla, Filippo Arrigoni, Nicola Toschi, Denis Peruzzo, Maria Grazia D’Angelo, Sandra Gandossini, Annamaria Russo, Eleonora Diella, Stefania Tirelli, Roberto Salati, Alessandra Rufini, Ivano Condo, Roberto Testi and Andrea Martinuzzi; Front. Neurosci., 09 October 2020; doi:10.3389/fnins.2020.00872 

Advanced MRI imaging (diffusion tensor imaging, DTI; functional MRI, fMRI; and resting-state fMRI, rs-fMRI) and retinal imaging (optical coherence tomography, OCT) were tested longitudinally in a small group of Friedreich’s ataxia patients participating in an open-label clinical trial testing the safety and the efficacy of 6-month treatment with interferon gamma. Preliminary data encourage the use of MRI, in particular fMRI, as a non-invasive method to monitor treatment response in FRDA and to achieve a better understanding of the physiology behind the observed treatment-induced effects.

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

ClinicalTrials.gov Identifier: NCT04577352

Randomized, Parallel-Arm, Double-Blind, Placebo-Controlled Study With Open-Label Extension to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Friedreich Ataxia (MOVE-FA).

Lead Sponsor: PTC Therapeutics. Start Date November 17, 2020, Phase 2/Phase 3, Location Countries: Australia, Canada, Italy, United States. The primary objective of the study is to evaluate the efficacy (using the modified Friedreich Ataxia Rating Scale [mFARS]) and safety of vatiquinone in participants with Friedreich ataxia (FA).

Neurodegenerative Diseases and the Auditory-Vestibular System

Mehta, Zarin PhD; Hale, Troy AuD; McMillan, Raechal BS; Sudaj, Gabriel BS; Pullman, Kelly AuD; Belus, Gail AuD; The Hearing Journal: October 2020 - Volume 73 - Issue 10 - p 38,40,41 doi: 10.1097/01.HJ.0000719804.32573.ea

Physicians and audiologists should consider auditory-vestibular dysfunction in patients with neurodegenerative diseases even when peripheral hearing sensitivity is normal.

Recapitulating the frataxin activation mechanism in an engineered bacterial cysteine desulfurase supports the architectural switch model

Shachin Patra, Cheng-Wei Lin, Manas K. Ghosh, Steven M. Havens, Seth A. Cory, David H. Russell, David P. Barondeau bioRxiv 2020.10.06.326603; doi:10.1101/2020.10.06.326603

Overall, these studies indicate a weakening of the homodimeric interface was a key development during the evolution of the eukaryotic system and provide new insights into the role of FXN.

Expanding the genotype–phenotype correlation of childhood sensory polyneuropathy of genetic origin

Samya Chakravorty, Rachel Logan, Molly J. Elson, Rebecca R. Luke & Sumit Verma; Sci Rep 10, 16184 (2020). doi:10.1038/s41598-020-73219-5 

Our single-center study shows genetic sensory polyneuropathies associated with progressive neurodegenerative disorders such as mitochondrial ataxia, Friedreich ataxia, spinocerebellar ataxia type 2, ataxia telangiectasia, spastic paraplegia, giant axonal neuropathy, and fumarate hydratase deficiency.

Emerging therapies in Friedreich's Ataxia

Zesiewicz TA, Hancock J, Ghanekar SD, Kuo SH, Dohse CA, Vega J. ; Expert Rev Neurother. 2020 Sep 21:1-14. doi:10.1080/14737175.2020.1821654. 

Areas covered include past and emerging therapies for FRDA, including antioxidants and mitochondrial-related agents, nuclear factor erythroid-derived 2-related factor 2 (Nrf2) activators, deuterated polyunsaturated fatty acids, iron chelators, histone deacetylase (HDAC) inhibitors, trans-activator of transcription (TAT)-frataxin, interferon gamma (IFNγ), erythropoietin, resveratrol, gene therapy, and anti-sense oligonucleotides (ASOs), among others.