LEXEO Therapeutics Receives Rare Pediatric Disease Designation and Orphan Drug Designation for LX2006 for the Treatment of Friedreich’s Ataxia

NEW YORK, June 30, 2021 (GLOBE NEWSWIRE) -- LEXEO Therapeutics, a clinical-stage gene therapy company, today announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease designation and Orphan Drug designation to LX2006 for the treatment of Friedreich’s ataxia (FA). LX2006 is an IV-administered, adeno-associated virus (AAV)-mediated gene therapy encoding the human frataxin gene. The designations granted to LX2006 cover cardiac disease and broader symptoms associated with FA.

LEXEO plans to initiate a Phase I/II clinical trial of LX2006 in patients with cardiomyopathy associated with FA in 2021.

Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene

Simge Kelekçi, Deniz Uğurlu-Çimen, Deniz Ata, Burcu Özçimen, Abdullah Burak Yıldız, Mehmet Batuhan Karakuş, Esra Börklü Yücel, Tamer T. Önder, Stem Cell Research, 2021, 102438, doi:10.1016/j.scr.2021.102438. 

In this present study, we generated induced pluripotent stem cells (iPSC) lines from fibroblasts of three unrelated FRDA patients using integration-free episomal vectors. All iPSC lines express the pluripotency markers such as OCT4 and SSEA4, display normal karyotypes and can differentiate into all three germ layers via in vivo teratoma formation assay.

Friedreich Ataxia: Multidisciplinary Clinical Care

Lynch DR, Schadt K, Kichula E, McCormack S, Lin KY., J Multidiscip Healthc 2021;14:1645-1658 doi:10.2147/JMDH.S292945 

This review provides a summary of the diverse manifestation of FRDA, existing symptomatic therapies, and approaches for integrative care for future therapy in FRDA.

The cardiomyopathy of Friedreich's ataxia common in a family: A case report

Amini O, Lakziyan R, Abavisani M, Sarchahi Z. Ann Med Surg (Lond). 2021 May 24;66:102408. doi: 10.1016/j.amsu.2021.102408. 

Because early diagnosis of the disease is difficult, clinical signs and the patient's current profile at the time of referral will be very helpful.

New biotech kid on the block making news

June 17, 2021. Capsida Biotherapeutics, a Newbury Park-based startup that recently raised $140 million in Series A funding, is partnering with a high-profile biotech company to develop treatment for Lou Gehrig’s disease (amyotrophic lateral sclerosis) and Friedreich’s ataxia, another neurodegenerative disease. CRISPR, a publicly traded company valued at around $9 billion, will lead the Friedreich’s ataxia program, and Capsida will lead the ALS program. Should their efforts be successful, the companies would equally share all research, development and commercialization costs and profits worldwide related to the collaboration product, according to the release.

Inicio Ronda de Inversión Biointaxis con Capital Cell

06.17.2021. Biointaxis es una spin-off biotecnológica surgida del Instituto de Investigación Germans Trias i Pujol (IGTP) y del grupo farmacéutico multinacional Gentec S.A. en 2018 establecida en el campus de Can Ruti de Badalona.

Nuestro objetivo en Biointaxis es llevar el fármaco de terapia génica BTX-101 que ha demostrado unos perfiles de seguridad y eficacia excelentes en 2 modelos de ratón de la enfermedad, uno crónico y otro agudo, al tratamiento curativo del paciente con Ataxia de Friedreich. La ataxia de Friedreich es una enfermedad hereditaria actualmente incurable que está causada por los déficits de la proteína frataxina. Con esta ronda de inversión Biointaxis con Capital Cell demostrará la seguridad y biodistribución adecuadas en primates no humanos para solicitar a la Agencia Europea del Medicamento su autorización para la fase clínica en pacientes con la enfermedad.

CRISPR Therapeutics and Capsida Biotherapeutics Announce Strategic Collaboration to Develop Gene-Edited Therapies for Amyotrophic Lateral Sclerosis and Friedreich’s Ataxia

ZUG, Switzerland and CAMBRIDGE, Mass. and THOUSAND OAKS, Calif., June 15, 2021 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on developing transformative gene-based medicines for serious diseases, and Capsida Biotherapeutics Inc., a biotechnology company dedicated to developing breakthrough gene therapies using fully integrated adeno-associated virus (AAV) engineering, cargo development and manufacturing, today announced a strategic partnership to research, develop, manufacture and commercialize in vivo gene editing therapies delivered with engineered AAV vectors for the treatment of familial amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia.

A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's Ataxia

Oscar A Campos, Narsis Attar, Nathan V Mallipeddi, Chen Cheng, Maria Vogelauer, Stefan Schmollinger, Sabeeha S Merchant, Siavash K Kurdistani; bioRxiv 2021.06.14.448268; doi:10.1101/2021.06.14.448268 

Campos OA, Attar N, Cheng C, Vogelauer M, Mallipeddi NV, Schmollinger S, Matulionis N, Christofk HR, Merchant SS, Kurdistani SK. A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's ataxia. Sci Adv. 2021 Dec 17;7(51):eabj9889. doi: 10.1126/sciadv.abj9889. Epub 2021 Dec 17.

Disruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad range of proteins, cause widespread cellular defects resulting in human disease. An underappreciated source of damage to Fe-S clusters are cuprous (Cu1+) ions. Since histone H3 enzymatically produces Cu1+ to support copper-dependent functions, we asked whether this activity could become detrimental to Fe-S clusters. Here, we report that histone H3-mediated Cu1+ toxicity is a major determinant of cellular Fe-S cluster quotient. Inadequate Fe-S cluster supply, either due to diminished assembly as occurs in Friedreich's Ataxia or defective distribution, causes severe metabolic and growth defects in S. cerevisiae. Decreasing Cu1+ abundance, through attenuation of histone cupric reductase activity or depletion of total cellular copper, restored Fe-S cluster-dependent metabolism and growth. Our findings reveal a novel interplay between chromatin and mitochondria in Fe-S cluster homeostasis, and a potential pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S cluster dysfunction.

Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA) (ARTEMIS)

ClinicalTrials.gov Identifier: NCT04921930; Sponsor: Institut National de la Santé Et de la Recherche Médicale, France Collaborator: Imagine Institute 

This dose-escalation study is aimed at investigating a novel application for artesunate in the treatment of Friedreich ataxia. It will evaluate this novel application of oral artesunate using a surrogate biological marker as primary endpoint in a phase I-II open trial.

Automatic speech recognition in neurodegenerative disease

Authors: Benjamin G. Schultz, Venkata S. Aditya Tarigoppula, Gustavo Noffs, Sandra Rojas, Anneke van der Walt, David B. Grayden, Adam P. Vogel; International Journal of Speech Technology, doi:10.1007/s10772-021-09836-w 

Automatic speech recognition (ASR) could potentially improve communication by providing transcriptions of speech in real time. ASR is particularly useful for people with progressive disorders that lead to reduced speech intelligibility or difficulties performing motor tasks. ASR services are usually trained on healthy speech and may not be optimized for impaired speech, creating a barrier for accessing augmented assistance devices. We tested the performance of three state-of-the-art ASR platforms on two groups of people with neurodegenerative disease and healthy controls. We further examined individual differences that may explain errors in ASR services within groups, such as age and sex. Speakers were recorded while reading a standard text. Speech was elicited from individuals with multiple sclerosis, Friedreich’s ataxia, and healthy controls. Recordings were manually transcribed and compared to ASR transcriptions using Amazon Web Services, Google Cloud, and IBM Watson.

Blindness and Deafness – an Extreme Phenotype in Friedreich Ataxia

Joana Damásio, Ana Sardoeira, Maria Araújo, Isabel Carvalho, Jorge Sequeiros, José Barros; Research Square; 2021. DOI: 10.21203/rs.3.rs-573040/v1. 

Severe vision loss and extreme deafness has been described in very few patients with Friedreich ataxia. Long duration, severe disease and large expanded alleles may account for such an extreme phenotype; nonetheless, the role of factors as modifying genes warrants further investigation in this subset of patients.

Luz verde a un ensayo clínico con calcitriol para validar su potencial terapéutico para tratar la Ataxia de Friedreich

Comunicación y Prensa IRBLleida; Lunes, 7 de junio de 2021

Un ensayo clínico podría validar el uso del calcitriol, la forma activa de la vitamina D, para tratar la Ataxia de Friedreich, tal como propone el grupo de investigación Bioquímica del Estrés Oxidativo del Instituto de Investigación Biomédica de Lleida (IRBLleida) y la Universidad de Lleida (UdL). Su investigación es la base de este ensayo que realizarán la Unidad de Ataxias del Hospital Josep Trueta de Girona y del Hospital Santa Caterina del Parc Hospitalari Martí i Julià de Salt conjuntamente con el Instituto de Investigación Biomédica de Girona (IDIBGI).

A clinical trial with calcitriol has begun to validate its therapeutic potential for treating Friedreich's Ataxia

Biotech-spain.com; 07/06/2021 

A clinical trial could validate the use of calcitriol, the active form of vitamin D, to treat Friedreich's Ataxia, as proposed by the Biochemistry of Oxidative Stress Group at the Biomedical Research Institute of Lleida (IRBLleida) and the University of Lleida (UdL). Their research is the basis of this trial to be carried out by the Ataxia Unit of the Josep Trueta Hospital in Girona and the Santa Caterina Hospital of the Parc Hospitalari Martí i Julià de Salt in conjunction with the Institute for Research in Biomedicine of Girona (IDIBGI).

6 Clinical presentation and outcomes of childhood hypertrophic cardiomyopathy associated with friedreich’s ataxia: a national cohort study

Rance T, Norrish G; Heart 2021;107:A5. doi:10.1136/heartjnl-2021-BCS.

This national study of childhood FA-HCM is the largest cohort reported to date and describes a high prevalence of atrial arrhythmias and early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM but no patients died suddenly.

Quantitative Assessment of Friedreich Ataxia via Self-Drinking Activity

R. Krishna, P. N. Pathirana, M. K. Horne, L. A. Corben and D. J. Szmulewicz; IEEE Journal of Biomedical and Health Informatics, vol. 25, no. 6, pp. 1985-1996, June 2021, doi: 10.1109/JBHI.2021.3069007. 

Effective monitoring of the progression of neurodegenerative conditions can be significantly improved by objective assessments. Clinical assessments of conditions such as Friedreich's Ataxia (FA), currently rely on subjective measures commonly practiced in clinics as well as the ability of the affected individual to perform conventional tests of the neurological examination. In this study, we propose an ataxia measuring device, in the form of a pressure canister capable of sensing certain kinetic and kinematic parameters of interest to quantify the impairment levels of participants particularly when engaged in an activity that is closely associated with daily living. In particular, the functional task of simulated drinking was utilised to capture characteristic features of disability manifestation in terms of diagnosis (separation of individuals with FA and controls) and severity assessment of individuals diagnosed with the debilitating condition of FA. Time and frequency domain analysis of these biomarkers enabled the classification of individuals with FA and control subjects to reach an accuracy of 98% and a correlation level reaching 96% with the clinical scores.

Coexistence of Tyrosinemia and Friedreich Ataxia in a Single Patient: Treatment with Liver Transplantation

Diya Cherian, Kimberly Schadt, Courtney Park, Stephanie Veasey, David Goldberg, David Lynch; Ann Case Report 6: 581. DOI: 10.29011/2574-7754.100581

Here we describe a young woman with coincidental presence of both FRDA and HT1, focusing on possible interactions between HT1 and FRDA, as well as her treatment by liver transplantation.

Rescue of central and peripheral neurological phenotype of friedreich's ataxia by intravenous delivery

Application US16/651,617- Assigned to VOYAGER THERAPEUTICS, INC. 

Described herein are compositions and methods for treating Friedreich's Ataxia (FA) using adeno-associated virus (AAV) to deliver therapeutics agents.

AavantiBio lands manufacturing partner in Friedreich's Ataxia program; NC Research Triangle lands another CDMO

June 3, 2021. ENDPOINTNEWS. AavantiBio and Resilience have announced a collaboration to manufacture a pipeline of therapies, including AavantiBio’s Friedreich’s Ataxia program, the company announced Thursday. 

The new facility will double its existing footprint, and support development, clinical and small-scale commercial manufacturing. The site is just a few miles from its current office, and will meet all FDA, EMA and GMP requirements, the company said.

FARA FA Pipeline Webinar - Jun 2, 2021

Molecular Details of the Frataxin–Scaffold Interaction during Mitochondrial Fe–S Cluster Assembly

Campbell, C.J.; Pall, A.E.; Naik, A.R.; Thompson, L.N.; Stemmler, T.L.; Int. J. Mol. Sci. 2021, 22, 6006. doi:10.3390/ijms22116006

Molecular Details of the Frataxin–Scaffold Interaction during Mitochondrial Fe–S Cluster Assembly

Results of a randomized double-blind study evaluating luvadaxistat in adults with Friedreich ataxia

Hao Wang, Jonathan Norton, Lin Xu, Nicholas DeMartinis, Rohini Sen, Ankit Shah, Jennifer Farmer, David Lynch; Annals of Clinical and Translational Neurology. 2021 May. DOI: 10.1002/acn3.51373.

Luvadaxistat (also known as TAK-831; NBI-1065844) was safe and well tolerated in this cohort of adults with FRDA; however, it did not demonstrate efficacy as a treatment for this condition.