Coronary Artery Disease in Patients With Friedreich's Ataxia

ClinicalTrials.gov Identifier: NCT04649866. Vasculopathy and Remodeling of Coronary Arteries in FRDA Patients.

Patients with HCM can then develop pulmonary hypertension (PH), a deadly condition of the blood vessels of the lung. While most of the research in FRDA has focused on nerves and heart muscle, alterations in blood vessels of the heart and lung may worsen disease in FRDA. But, the role of FXN in these blood vessels has never been defined.Our pilot data suggest that Frataxin (FXN ) deficiency can control senescence and downstream function in various types of Endothelial cells (ECs), we hypothesize that Friedreich's Ataxia (FRDA) patients may demonstrate endothelial cells EC abnormalities throughout the vasculature potentially before overt cardiomyopathy develops.

Afrontamiento familiar ante el diagnóstico y evolución de la enfermedad ataxia de Friedreich, «Family dealing with the diagnosis and evolution of Friedreich’s ataxia disease»

Erika E. López Rios, Yeisy C., Guarate Coronado; Ocronos. Vol. III. Nº 8– Diciembre 2020. Pág. Inicial: Vol. III; nº8:12; ORCID iD: http://orcid.org/ 0000-0003-1526-4693

A partir del diagnóstico y evolución de la Ataxia de Friedreich los familiares experimentaron sentimientos negativos, surgieron cambios a nivel económico, familiar, social y calidad de vida, además el cuidado resulta difícil, por lo que el cuidador principal presentó sobrecarga. Sin embargo, la familia ha logrado afrontar positivamente utilizando estrategias enfocadas al problema y emociones. Conclusiones: La familia utilizó estrategias de afrontamiento enfocadas en las emociones y centradas en el problema, pues emplearon el autocontrol emocional, aceptación de responsabilidades, reevaluación positiva, apoyo familiar y espiritual, búsqueda de información sobre la enfermedad y alternativas de tratamiento.

Ferroptosis: molecular mechanisms and health implications

Daolin Tang, Xin Chen, Rui Kang, Guido Kroemer; Cell Res (2020). doi:10.1038/s41422-020-00441-1

The ferroptosis inhibitor SRS11-92 is highly effective in protecting human primary fibroblasts from cell death induced by frataxin depletion, indicating that targeting ferroptosis might be useful for the treatment of Friedreich ataxia, pending confirmation in animal models.

Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults

Picca, A.; Saini, S.K.; Mankowski, R.T.; Kamenov, G.; Anton, S.D.; Manini, T.M.; Buford, T.W.; Wohlgemuth, S.E.; Xiao, R.; Calvani, R.; Coelho-Júnior, H.J.; Landi, F.; Bernabei, R.; Hood, D.A.; Marzetti, E.; Leeuwenburgh, C; Cells 2020, 9, 2579. doi:10.3390/cells9122579

An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

PTC Therapeutics Announces Initiation of Global Phase 3 Clinical Trial to Evaluate Vatiquinone in Friedreich Ataxia

SOUTH PLAINFIELD, N.J., Nov. 30, 2020 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT), today announced the initiation of the registration-directed Phase 3 MOVE-FA study evaluating vatiquinone (PTC743) in children and young adults with Friedreich ataxia (FA) The Phase 3 MOVE-FA trial is an 18-month parallel arm, placebo-controlled study evaluating vatiquinone versus placebo in approximately 110 children and young adults with FA. The primary endpoint is the change from baseline in the modified Friedreich ataxia rating scale (mFARS), with key secondary endpoints assessing ambulation and activities of daily living. This endpoint strategy was developed in consultation with both the FDA and European Medicines Agency. The study will include sites in the U.S., E.U., Australia and Latin America.

FDA sends Reata back to the drawing board

Evaluate Vantage, Madeleine Armstrong, November 25, 2020

The need for another pivotal trial of omaveloxolone in Friedreich's ataxia looks increasingly likely. This result for omaveloxolone was not entirely unexpected; Reata said during its second-quarter results that the FDA had asked for a second pivotal trial to support the Moxie study. Part two of Moxie was declared a success, but only after Reata switched endpoints to increase its chances after the first part failed (Reata looks to outsmart Abbvie again, October 15, 2019).

Overview of Friedreich's ataxia models: Comparison of frataxin protein levels and phenotype

27 November 2020. The Jackson Laboratory .

Watch this presentation from Dr. Cat Lutz, Senior Director of Mouse Repository & In Vivo Pharmacology at The Jackson Laboratory, titled: Overview of Friedreich's ataxia models: Comparison of frataxin protein levels and phenotype. This talk was presented at the SelectScience® Virtual Neuroscience Summit.

https://www.selectscience.net/SelectScience-TV/Videos/overview-of-friedreichs-ataxia-models-comparison-of-frataxin-protein-levels-and-phenotype/?videoID=5178

Central Nervous System Therapeutic Targets in Friedreich Ataxia

Dr. Ian Harding, Dr. David R Lynch, Dr. Arnulf Koeppen, and Dr. Massimo Pandolfo; Human Gene Therapy 0 0:ja; doi:10.1089/hum.2020.264

In general, the proprioceptive system appears to be affected early, while later in the disease the dentate nucleus of the cerebellum and, to some degree, the corticospinal tracts degenerate. In the current era of expanding therapeutic discovery in FRDA, including progress towards novel gene therapies, a deeper and more specific consideration of potential treatment targets in the nervous system is necessary. In the present work, we have re-examined the neuropathology of FRDA, recognizing new issues superimposed on classical findings and dissected the peripheral nervous system (PNS) and central nervous system (CNS) aspects of the disease and the affected cell types. Understanding the temporal course of neuropathological changes is needed to identify areas of modifiable disease progression and the CNS and PNS locations that can be targeted at different timepoints. As most major targets of long-term therapy are in the CNS, the present review uses multiple tools for evaluation of the importance of specific CNS locations as targets. In addition to clinical observations, the conceptualizations here include physiological, pathological and imaging approaches, and animal models. We believe that this review, through analysis of a more complete set of data derived from multiple techniques, provides a comprehensive summary of therapeutic targets in FRDA.

New drug confirmed as a potential therapeutic agent for a rare disease, Friedreich's Ataxia

http://biotech-spain.com , 25/11/2020, Fuente: IRB Lleida. Institut de Recerca Biomèdica.

It is the leriglitazone that improves the loss of frataxin, the cause of the disease .

A recent study has confirmed the benefits of the drug leriglitazone in treating Friedrich's Ataxia, a rare disease that affects 2-4 people in 100,000 and for which there is currently no effective cure. Research has confirmed that this drug improves the deficiencies of frataxin loss in cellular and animal models of Friedreich's Ataxia. This disease is caused by a deficiency in frataxin levels, which leads to mitochondrial dysfunction with neurological and cardiac involvement. The research has been published in the journal Neurobiology of Disease.

The research has been carried out in collaboration between the company Minoryx Therapeutics, the Oxidative stress biochemistry Stress Group of the University of Lleida (UdL) and the Institute of Biomedical Research of Lleida (IRBLleida), the Department of Physiology of the Faculty of Medicine and Dentistry of the University of Valencia - INCLIVA, the Centre for Biomedical Research Network on Rare Diseases (CIBERER) and the Department of Paediatrics and Neurology of The Children's Hospital of Philadelphia.

Confirman un nuevo fármaco como potencial agente terapéutico para tratar la ataxia de Friedreich

Universitat de València, GABINETE DE PRENSA, 25 noviembre de 2020.

La investigación ha confirmado los beneficios del fármaco leriglitazona para tratar la ataxia de Friedrich, una enfermedad rara que afecta a 2-4 personas de cada 100.000 y para la cual, actualmente, no hay una cura efectiva. La investigación es una colaboración entre el grupo de investigación que lidera Federico Pallardó, la empresa Minoryx Therapeutics, y el INCLIVA, perteneciente al Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), el Grupo de Investigación Bioquímica del Estrés Oxidativo, de la Universidad de Lleida (UdL) y el Instituto de Investigación Biomédica de Lleida (IRBLleida), y el Departamento de Pediatría y Neurología del The Children's Hospital of Philadelphia.