GSE261655 Frataxin Deficiency Drives a Shift from Mitochondrial Metabolism to Glucose Catabolism, Triggering an Inflammatory Phenotype in Microglia
This study highlights the effects of mitochondrial frataxin (FXN) depletion, which causes Friedreich's ataxia (FRDA), a neurodegenerative condition characterized by coordination and muscle control deficiencies. Using single-cell RNA sequencing, we identified specific cell groups in the cerebellum of a FRDA mouse model, emphasizing a notable inflammatory microglial response. These FXN-deficient microglia cells exhibited enhanced inflammatory reactions. Furthermore, our metabolomic analyses revealed increased glycolysis and itaconate production in these cells, possibly driving the inflammation. Remarkably, butyrate treatment...
Source: GEO: Gene Expression Omnibus - April 16, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
GSE261654 Frataxin Deficiency Drives a Shift from Mitochondrial Metabolism to Glucose Catabolism, Triggering an Inflammatory Phenotype in Microglia (scRNA-Seq)
This study highlights the effects of mitochondrial frataxin (FXN) depletion, which causes Friedreich's ataxia (FRDA), a neurodegenerative condition characterized by coordination and muscle control deficiencies. Using single-cell RNA sequencing, we identified specific cell groups in the cerebellum of a FRDA mouse model, emphasizing a notable inflammatory microglial response. These FXN-deficient microglia cells exhibited enhanced inflammatory reactions. Furthermore, our metabolomic analyses revealed increased glycolysis and itaconate production in these cells, possibly driving the inflammation. Remarkably, butyrate treatment...
Source: GEO: Gene Expression Omnibus - April 16, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
GSE261653 Frataxin Deficiency Drives a Shift from Mitochondrial Metabolism to Glucose Catabolism, Triggering an Inflammatory Phenotype in Microglia (bulk RNA-Seq)
This study highlights the effects of mitochondrial frataxin (FXN) depletion, which causes Friedreich's ataxia (FRDA), a neurodegenerative condition characterized by coordination and muscle control deficiencies. Using single-cell RNA sequencing, we identified specific cell groups in the cerebellum of a FRDA mouse model, emphasizing a notable inflammatory microglial response. These FXN-deficient microglia cells exhibited enhanced inflammatory reactions. Furthermore, our metabolomic analyses revealed increased glycolysis and itaconate production in these cells, possibly driving the inflammation. Remarkably, butyrate treatment...
Source: GEO: Gene Expression Omnibus - April 16, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Pharmacotherapeutic strategies for Friedreich Ataxia: a review of the available data
Expert Opin Pharmacother. 2024 Apr 15. doi: 10.1080/14656566.2024.2343782. Online ahead of print.ABSTRACTINTRODUCTION: Friedreich ataxia (FRDA) is a rare autosomal recessive disease, marked by loss of coordination as well as impaired neurological, endocrine, orthopedic, and cardiac function. There are many symptomatic medications for FRDA, and many clinical trials have been performed, but only one FDA-approved medication exists.AREAS COVERED: The relative absence of the frataxin protein (FXN) in FRDA causes mitochondrial dysfunction, resulting in clinical manifestations. Currently, the only approved treatment for FRDA is a...
Source: Expert Opinion on Pharmacotherapy - April 15, 2024 Category: Drugs & Pharmacology Authors: Katherine Gunther David R Lynch Source Type: research
Approval of omaveloxolone for Friedreich ataxia
Nature Reviews Neurology, Published online: 03 April 2024; doi:10.1038/s41582-024-00957-9The recent approval of omaveloxolone for the treatment of Friedreich ataxia in the USA and Europe represents an important milestone in the field of rare neurological diseases. However, many challenges lie ahead, including the translation of trial results into clinical practice, and the management of patients’ expectations. (Source: Nature Reviews Neurology)
Source: Nature Reviews Neurology - April 3, 2024 Category: Neurology Authors: Sylvia Boesch Elisabetta Indelicato Source Type: research
Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of S ão Paulo, Brazil
Cerebellum. 2024 Mar 23. doi: 10.1007/s12311-024-01687-w. Online ahead of print.ABSTRACTFriedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians. Prevalence was estimated dividing the number of patients by the population of the state as reported in the last census. Patients were invited to answer an onl...
Source: Cerebellum - March 23, 2024 Category: Neuroscience Authors: Daiana Suelen Machado Celiana Figueiredo Viana Jos é Luiz Pedroso Orlando Graziani Povoas Barsottini Pedro Jos é Tomaselli Wilson Marques Thiago J R Rezende Alberto R M Martinez Marcondes Cavalcante Fran ça Source Type: research
Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of S ão Paulo, Brazil
Cerebellum. 2024 Mar 23. doi: 10.1007/s12311-024-01687-w. Online ahead of print.ABSTRACTFriedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians. Prevalence was estimated dividing the number of patients by the population of the state as reported in the last census. Patients were invited to answer an onl...
Source: Cerebellum - March 23, 2024 Category: Neuroscience Authors: Daiana Suelen Machado Celiana Figueiredo Viana Jos é Luiz Pedroso Orlando Graziani Povoas Barsottini Pedro Jos é Tomaselli Wilson Marques Thiago J R Rezende Alberto R M Martinez Marcondes Cavalcante Fran ça Source Type: research
Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of S ão Paulo, Brazil
Cerebellum. 2024 Mar 23. doi: 10.1007/s12311-024-01687-w. Online ahead of print.ABSTRACTFriedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians. Prevalence was estimated dividing the number of patients by the population of the state as reported in the last census. Patients were invited to answer an onl...
Source: Cerebellum - March 23, 2024 Category: Neuroscience Authors: Daiana Suelen Machado Celiana Figueiredo Viana Jos é Luiz Pedroso Orlando Graziani Povoas Barsottini Pedro Jos é Tomaselli Wilson Marques Thiago J R Rezende Alberto R M Martinez Marcondes Cavalcante Fran ça Source Type: research
Exploring mitochondrial biomarkers for Friedreich's ataxia: a multifaceted approach
This study presents an in-depth analysis of mitochondrial enzyme activities in Friedreich's ataxia (FA) patients, focusing on the Electron Transport Chain complexes I, II, and IV, the Krebs Cycle enzyme Citrate Synthase, and Coenzyme Q10 levels. It examines a cohort of 34 FA patients, comparing their mitochondrial enzyme activities and clinical parameters, including disease duration and cardiac markers, with those of 17 healthy controls. The findings reveal marked reductions in complexes II and, specifically, IV, highlighting mitochondrial impairment in FA. Additionally, elevated Neurofilament Light Chain levels and cardio...
Source: Journal of Neurology - March 23, 2024 Category: Neurology Source Type: research
Accelerometer-based measures in Friedreich ataxia: a longitudinal study on real-life activity
Quantitative measurement of physical activity may complement neurological evaluation and provide valuable information on patients’ daily life. We evaluated longitudinal changes of physical activity in patients with Friedreich ataxia (FRDA) using remote monitoring with wearable sensors. We performed an observational study in 26 adult patients with FRDA and 13 age-sex matched healthy controls (CTR). Participants were asked to wear two wearable sensors, at non-dominant wrist and at waist, for 7 days during waking hours. Evaluations were performed at baseline and at 1-year follow-up. We analysed the percentage of time spent...
Source: Frontiers in Pharmacology - March 19, 2024 Category: Drugs & Pharmacology Source Type: research
Unique combinations of ultrasound and electrophysiological findings distinguish Friedreich's ataxia from other inherited ataxias
Clin Neurophysiol. 2024 Mar 7;161:157-158. doi: 10.1016/j.clinph.2024.02.035. Online ahead of print.NO ABSTRACTPMID:38492270 | DOI:10.1016/j.clinph.2024.02.035 (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - March 16, 2024 Category: Neurology Authors: Luciana Pelosi Eoin Mulroy Ruth Leadbetter Miriam Rodrigues Richard Roxburgh Source Type: research
Unique combinations of ultrasound and electrophysiological findings distinguish Friedreich's ataxia from other inherited ataxias
Clin Neurophysiol. 2024 Mar 7;161:157-158. doi: 10.1016/j.clinph.2024.02.035. Online ahead of print.NO ABSTRACTPMID:38492270 | DOI:10.1016/j.clinph.2024.02.035 (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - March 16, 2024 Category: Neurology Authors: Luciana Pelosi Eoin Mulroy Ruth Leadbetter Miriam Rodrigues Richard Roxburgh Source Type: research
Unique combinations of ultrasound and electrophysiological findings distinguish Friedreich's ataxia from other inherited ataxias
Clin Neurophysiol. 2024 Mar 7;161:157-158. doi: 10.1016/j.clinph.2024.02.035. Online ahead of print.NO ABSTRACTPMID:38492270 | DOI:10.1016/j.clinph.2024.02.035 (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - March 16, 2024 Category: Neurology Authors: Luciana Pelosi Eoin Mulroy Ruth Leadbetter Miriam Rodrigues Richard Roxburgh Source Type: research
Generation of two human induced pluripotent stem cell lines, IGIBi012-A and IGIBi013-A from Friedreich's ataxia (FRDA) patients with homozygous GAA repeat expansion in FXN gene
Stem Cell Res. 2024 Feb 10;76:103340. doi: 10.1016/j.scr.2024.103340. Online ahead of print.ABSTRACTFriedreich's ataxia is a neurodegenerative disorder caused by the hyper expansion of (GAA-TTC)n triplet repeats in the first intron of the FXN gene. Here, we generated iPSC lines from two individuals with FRDA, both of whom have homozygous GAA repeat expansion in the first intron of FXN gene. Both iPSC lines demonstrated characteristics of pluripotency, including expression of pluripotency markers, stable karyotypes and ability to develop into all three germ layers, and presence of GAA repeat expansion with reduced FXN mRNA ...
Source: Cell Research - February 17, 2024 Category: Cytology Authors: Istaq Ahmad Himanshi Kapoor Achal Kumar Srivastava Mohammed Faruq Source Type: research
Nerve ultrasound in Friedreich's Ataxia: enlarged nerves as a biomarker of disease severity
CONCLUSIONS: Our study shows that high-resolution ultrasound reveals notable nerve abnormalities, primarily in the upper limbs of patients diagnosed with Friedreich's Ataxia. The observed correlation between these nerve abnormalities and clinical disability scales indicates the potential use of this technique as a biomarker for evaluating disease severity and treatment effects.SIGNIFICANCE: Nerve Ultrasound is a potential biomarker of disease severity in Friedreich's Ataxia.PMID:38359552 | DOI:10.1016/j.clinph.2024.01.004 (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - February 15, 2024 Category: Neurology Authors: G Di Pietro E Cioffi P Falco E Galosi G De Stefano G Di Stefano C Leone V Martines S Perotti C Casali A Truini Source Type: research
