European Investment Bank provides Minoryx with up to €25 million to support development of breakthrough therapies in orphan neurodegenerative diseases

Press release, 30 October 2020, Barcelona.

 The European Investment Bank (EIB) today announced that it has approved €25 million financing for Minoryx Therapeutics, a Phase 3 clinical stage biotech company focused on the development of differentiating treatment options for orphan central nervous system (CNS) disorders.

The EU bank will grant long-term financing to Minoryx to drive the company's research activities in orphan genetic diseases for which there are currently no approved drugs available. The EIB investments will specifically support the development of Minoryx's leriglitazone, a disease-modifying treatment (PPAR-γ agonist) currently being evaluated in three late-stage clinical trials:......Phase 2 FRAMES study in Friedreich's Ataxia (FRDA), a life threatening disease characterised by neurodegeneration resulting in loss of coordination, muscle strength, and cardiomyopathy.

EL BANCO EUROPEO DE INVERSIONES PROPORCIONA €25M A MINORYX PARA APOYAR EL DESARROLLO DE TERAPIAS INNOVADORAS EN ENFERMEDADES RARAS NEURODEGENERATIVAS.

Mataró (Barcelona, España) y Charleroi (Bélgica), 30 de octubre de 2020. Minoryx Therapeutics, una empresa biotecnológica en fase clínica III especializada en el desarrollo de tratamientos diferenciales para enfermedades raras del sistema nervioso central (CNS), ha anunciado hoy que el Banco Europeo de Inversiones (BEI) ha aprobado una financiación de 25 millones de euros. El banco de la UE concederá financiación a largo plazo a Minoryx para impulsar las actividades de investigación y desarrollo de la entidad en enfermedades genéticas huérfanas para las que actualmente no se dispone de medicamentos aprobados.

 Las inversiones del BEI apoyarán específicamente el desarrollo de la leriglitazona, un agonista PPAR gamma diferenciado y con potencial de modificar el curso de la enfermedad que actualmente se está evaluando en tres ensayos clínicos en fase avanzada. Estudio FRAMES de fase II en ataxia de Friedreich (FRDA).

30/10/2020. ACN Mataró.-El Banc Europeu d’Inversions (BEI) ha anunciat l’aprovació de 25 milions d’euros en finançament per a Minoryx Therapeutics, una empresa de biotecnologia amb seu a Mataró que es dedica al desenvolupament de noves opcions terapèutiques per a malalties del sistema nerviós central per a les que no hi ha medicaments aprovats, com l’adrenomieloneuropatia, l’adrenoleucodistròfia o l’atàxia de Friedreich. BEI da 25 millones a firma que desarrolla terapia para enfermedades genéticas. Barcelona, 30 oct (EFE).- 

El Banco Europeo de Inversiones (BEI) ha anunciado que financiará con 25 millones de euros a Minoryx Therapeutics, una empresa de biotecnología centrada en el desarrollo de nuevas terapias para enfermedades genéticas huérfanas del sistema nervioso central y con sede en el Tecnocampus de Mataró (Barcelona). El ensayo (FRAMES) estudia la ataxia de Friedreich (AF), una enfermedad potencialmente mortal caracterizada por una neurodegeneración que provoca pérdida de coordinación y de fuerza muscular y cardiomiopatía.

 

[4Fe-4S] cluster trafficking mediated by Arabidopsis mitochondrial ISCA and NFU proteins

Tamanna Azam, Jonathan Przybyla-Toscano, Florence Vignols, Jérémy Couturier, Nicolas Rouhier, and Michael K. Johnson, J. Biol. Chem. jbc.RA120.015726. doi:10.1074/jbc.RA120.015726

 The results demonstrate rapid, unidirectional and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

An Overview of the Ferroptosis Hallmarks in Friedreich’s Ataxia

Turchi, R.; Faraonio, R.; Lettieri-Barbato, D.; Aquilano, K. Biomolecules 2020, 10, 1489. doi:10.3390/biom10111489 

 Even though ferroptosis has been associated with various neurodegenerative diseases including FRDA, the mechanisms leading to disease onset/progression have not been demonstrated yet. We describe the molecular alterations occurring in FRDA that overlap with those characterizing ferroptosis. Major conclusions: The study of ferroptotic pathways is necessary for the understanding of FRDA pathogenesis, and anti-ferroptotic drugs could be envisaged as therapeutic strategies to cure FRDA.

Gene Therapy Company AavantiBio Launches With $107 Million Series A Financing From Perceptive Advisors, Bain Capital Life Sciences, RA Capital Management and Sarepta Therapeutics

CAMBRIDGE, Mass., Oct. 22, 2020 (GLOBE NEWSWIRE). 

 A premier syndicate of life sciences investors including Perceptive Advisors, Bain Capital Life Sciences (“Bain Capital”), and RA Capital Management (“RA Capital”) (collectively the “Investor Group”) together with Sarepta Therapeutics, Inc. (“Sarepta”) (NASDAQ: SRPT), a leader in precision genetic medicine for rare diseases, today announced a $107 million Series A financing to create AavantiBio, a gene therapy company focused on transforming the lives of patients with rare genetic diseases. The private financing round includes a $15 million equity investment from Sarepta.

Headquartered in the greater Boston area, UF startup and UF Innovate | The Hub resident client AavantiBio, is co-founded by renowned gene therapy researchers Barry Byrne, M.D., Ph.D., and Manuela Corti, P.T., Ph.D., who together bring thirty years of experience to the company. AavantiBio’s lead program is in Friedreich’s Ataxia (FA), a rare inherited genetic disease that causes cardiac and central nervous system dysfunction. AavantiBio’s research efforts expand on foundational research conducted by Drs. Byrne and Corti in Friedreich’s Ataxia, among other rare genetic disorders. AavantiBio will benefit from strategic partnerships with the University of Florida’s renowned Powell Gene Therapy Center and the MDA Care Center at UF Health where Drs. Byrne and Corti maintain their research and clinical practices. Initial funding in AavantiBio was provided by GoFAR, an Italian patient advocacy group, and the Muscular Dystrophy Association Venture Philanthropy Fund.

The French Association of Ataxia in Friedreich renews its 25,000 euro grant to validate the therapeutic potential of calcitriol for treating this rare malaltia

IRBLleida, Friday, October 23, 2020. The French Association of Ataxia of Friedreich has renewed the aid of 25,000 euros to the Oxidative stress biochemistry Research Group of the Biomedical Research Institute of Lleida (IRBLleida) and the University of Lleida (UdL) to validate the therapeutic potential of calcitriol, the active form of vitamin D, to treat this disease. "The entity has decided to continue collaborating due to the advances in research carried out in Lleida, despite the difficulties of working in the laboratory during the confinement and the new normality" explained the principal investigator of this project, Fabien Delaspre.

Sarepta, continuing its gene therapy push, helps launch a startup

BIOPHARMA DIVE, Oct. 22, 2020. AavantiBio joins a couple large, powerful companies in the hunt for a gene therapy to treat Friedreich's ataxia. Pfizer and Novartis are each working on their own programs. Outside of gene therapy, Reata Pharmaceuticals disclosed last year positive data from a study that tested an oral drug, known as omaveloxolone, in patients with Friedreich's ataxia. Reata said it intends to file the drug for approval based on those results.

Design Therapeutics Appoints Industry Veteran, Dr. João Siffert, as Chief Executive Officer

Design Therapeutics. San Diego, Calif., Oct. 20, 2020

Design Therapeutics, a biotechnology company developing a platform of gene targeted chimera (GeneTAC™) small molecules for the treatment of serious degenerative disorders caused by nucleotide repeat expansions, today announced that João Siffert, M.D., has been appointed as chief executive officer and will also join the Board of Directors. Dr. Siffert joins the founding Design Therapeutics team, including Pratik Shah, Ph.D., co-founder and executive chairman; Aseem Ansari, Ph.D., co-founder and director; and Sean Jeffries, Ph.D., chief business officer. Dr. Siffert brings extensive industry knowledge to Design, with 30 years combined experience in the biopharmaceutical industry, clinical practice and academia. 

 Design Therapeutics is a biotechnology company developing a new class of therapies based on a platform of gene targeted chimera (GeneTAC™) small molecules. The company’s lead program is focused on the treatment of Friedreich ataxia and discovery efforts are ongoing in other for serious degenerative disorders caused by nucleotide repeat expansions.

Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations

Perez-Lloret S, van de Warrenburg B, Rossi M, Rodríguez-Blázquez C, Zesiewicz T, Saute JAM, Durr A, Nishizawa M, Martinez-Martin P, Stebbins GT, Schrag A, Skorvanek M; and members of the MDS Rating Scales Review Committee; Mov Disord. 2020 Oct 6. doi: 10.1002/mds.28313

We identified some "recommended" scales and functional tests for the assessment of patients with major hereditary ataxias and other cerebellar disorders. The main limitations of these instruments include the limited assessment of patients in the more severe end of the spectrum and children. Further research in these populations is warranted.

Safety and Efficacy of Omaveloxolone in Friedreich's Ataxia (MOXIe Study)

Lynch, D.R., Chin, M.P., Delatycki, M.B., Subramony, S., Corti, M., Hoyle, J.C., Boesch, S., Nachbauer, W., Mariotti, C., Mathews, K.D., Giunti, P., Wilmot, G., Zesiewicz, T., Perlman, S., Goldsberry, A., O'Grady, M. and Meyer, C.J. (2020). Ann Neurol. Accepted Author Manuscript. doi:10.1002/ana.25934

In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FRDA.

Reata Pharma Accused in Securities Suit of Hyping Drug Prospects

PHILADELPHIA, Oct. 16, 2020 (GLOBE NEWSWIRE) -- Kehoe Law Firm, P.C. is investigating potential securities claims on behalf of investors of Reata Pharmaceuticals, Inc. (“Reata” or the “Company”) (NASDAQ: RETA) to determine whether the Company engaged in securities fraud or other unlawful business practices. Omaveloxolone, according to the complaint, is “[a]mong Reata’s drug candidates under development . . . which is in Phase 2 clinical development to treat Friedreich’s ataxia (‘FA’). Following the announcement of positive data from the MOXIe Part 2 study of omaveloxolone for FA in October 2019, the Company represented that it would seek submission for marketing approval of omaveloxolone for the treatment of FA in the [United States] with the U.S. Food and Drug Administration (‘FDA’).” The Reata Defendants, according to the complaint, made false and/or misleading statements and/or failed to disclose that: (i) the MOXIe Part 2 study results were insufficient to support a single study marketing approval of omaveloxolone for the treatment of FA in the United States without additional evidence.

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.

Mechanism of Iron–Sulfur Cluster Assembly: In the Intimacy of Iron and Sulfur Encounter

Srour, B.; Gervason, S.; Monfort, B.; D’Autréaux, B. . Inorganics 2020, 8, 55.   doi:10.3390/inorganics8100055

In this paper, we review the most recent advances on the mechanism of assembly for the founding member of the Fe–S cluster family, the [2Fe2S] cluster that is the building block of all other Fe–S clusters. The aim is to provide a survey of the mechanisms of iron and sulfur insertion in the scaffold proteins by examining how these processes are coordinated, how sulfide is produced and how the dinuclear [2Fe2S] cluster is formed, keeping in mind the question of the physiological relevance of the reconstituted systems. We also cover the latest outcomes on the functional role of the controversial frataxin protein in Fe–S cluster biosynthesis.

Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis

Jingjing Liu, Hui He, Jing Wang, Xiaoping Guo, Hongkun Lin, Huimin Chen, Chunjie Jiang, Li Chen, Ping Yao, Yuhan Tang, Toxicology, 2020, 152584, doi:10.1016/j.tox.2020.152584. Frataxin deficiency enhanced ferroptosis driven by ethanol via evaluating the levels of lactate dehydrogenase, cell morphological changes, mitochondrial labile iron pool, and lipid peroxidation. Conversely, restoring frataxin alleviated the sensitivity to ferroptosis. In addition, frataxin overexpression mitigated the sensitivity of ethanol-induced ferroptosis in HepG2CYP2E1+/+.