Clinical Ethics Consultation in Neurology – a case series

Benjamin Ilse, Bernd Alt-Epping, Albrecht Günther, Jan Liman & Alfred Simon; BMC Neurol 21, 216 (2021). doi:10.1186/s12883-021-02244-2 

The concept of clinical ethics consultation (CECs) was implemented to provide support in ethical controversies in clinical settings and are offered in at least every second hospital in Germany. Neurological disorders often require complex decision-making. The aims of this study were to determine which situations lead to CEC in neurology and to investigate the influence of the individual patient’s wishes on the recommendation.

Friedreich's ataxia researcher Associate Professor Mirella Dottori has received a funding boost

JULY 2 2021, Associate Professor Mirella Dottori, a researcher at the University of Wollongong will receive $982,861 over three years from the Medical Research Future Fund (MRFF) and National Health and Medical Research Council (NHMRC) for her ground-breaking research into Friedreich's ataxia.

 

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.