AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich Ataxia: A Nonrandomized Clinical Trial

Crystal RG, Weinsaft JW, Kaminsky SM, et al. AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich Ataxia: A Nonrandomized Clinical Trial. JAMA Cardiol. Published online June 17, 2026. doi:10.1001/jamacardio.2026.1699 

In an open-label, dose-ranging, nonrandomized clinical trial of 17 patients, intravenous administration of AAVrh.10hFXN was associated with minimal toxic effects, reduced cardiac magnetic resonance imaging assessment of left ventricular mass index, and reduced serum high-sensitivity troponin I level.

Seventeen patients with FA cardiomyopathy (mean [SD] age, 25 [6] years; 11 [65%] female) were followed up for a mean (SD) of 20 (8) months. There were 4 serious adverse events, 3 possibly related to prednisone immunosuppression and 1 possibly vector-related myocarditis 12 months after therapy, all of which resolved. Other adverse events were transient, nonserious, or not treatment related. In all 8 patients with cardiac biopsy 3 months after therapy, there were higher levels of cardiac FXN (dose cohort 1, 20%; cohort 2, 81%; cohort 3, 123%). After therapy, LVMI was lower by at least 10% in 9 patients and stabilized in 8 patients. Excluding the patient with myocarditis, posttherapy values of serum hs troponin I were lower by at least 10% in 15 patients and higher by at least 10% in 2 patients.

Polyphenols in mtDNA Repair, Mitochondrial Biogenesis, and Mitophagy: An Integrative Review

Victoria-Montesinos, D., Barcina-Pérez, P., García-Muñoz, A.M. (2026). Polyphenols in mtDNA Repair, Mitochondrial Biogenesis, and Mitophagy: An Integrative Review. BIOCELL, 50(6), 2. doi:10.32604/biocell.2026.077286 

 Mitochondrial dysfunction is a central hallmark of metabolic, hepatic, cardiovascular, and neurodegenerative diseases. Dietary polyphenols modulate mitochondrial pathways, but their integrated effects remain poorly appreciated. This narrative review synthesizes preclinical and clinical evidence on four polyphenols (resveratrol, epigallocatechin-3-gallate, quercetin, and oleuropein) and examines their mechanisms in mitochondrial biogenesis, mtDNA protection, and mitophagy. Experimental studies indicate that these compounds activate conserved adaptive pathways, including sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), AMP-activated protein kinase (AMPK), and PTEN-induced kinase 1 (PINK1) with Parkin, therapy enhancing mitochondrial biogenesis, reducing oxidative stress, and promoting selective removal of damaged mitochondria

Genetic modifiers of Friedreich's ataxia pathophysiology in Drosophila melanogaster - A systematic review and meta-analysis

Ravi Kant Yadav, Vishnu Swarup, Anami Ahuja, Dipesh Talukdar, Divyani Garg, Muraleedhar Aski, Achal Kumar Srivastava, Prachi Yadav, Genetic modifiers of Friedreich's ataxia pathophysiology in Drosophila melanogaster - A systematic review and meta-analysis, Free Radical Biology and Medicine, Volume 254, 2026, Pages 196-210,, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2026.06.031. 

 Ferritins overexpression, Miro inhibition, and catalase overexpression, converging pathways iron homeostasis, mitochondrial dynamics and oxidative stress management, were found to be the top ranked modifiers for their beneficial effects on FRDA pathophysiology and were suggested for further studies as therapeutic targets.

Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model

Lees, J.G., Zhang, H., Jiao, L. et al. Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model. Cell Death Dis (2026). doi:10.1038/s41419-026-09030-3

 RNA sequencing revealed a distinct transcriptional profile associated with frataxin deficiency. MEG3 and PCDHGA10 were consistently dysregulated across all three FRDA-iPSC lines and may represent early molecular markers of FRDA cardiomyopathy. Functional interrogation of these candidates demonstrated that targeted silencing of MEG3 or PCDHGA10 in FRDA cardiomyocytes significantly reduced disease‑associated cell death without affecting FXN expression. Notably, PCDHGA10 silencing also normalized elevated mitochondrial reactive oxygen species, whereas MEG3 silencing did not, highlighting gene‑specific contributions to FRDA cardiomyocyte survival. Collectively, these findings identify MEG3 and PCDHGA10 as functionally relevant regulators of FRDA cardiomyocyte pathology.

Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting

Ramchunder Z, Kalef-Ezra E, Suleman S ..., Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting, iScience, 2026; 29. DOI: 10.1016/j.isci.2026.116479 

 Sphingolipids are increasingly recognized for their roles in neurodegeneration with emerging evidence indicating their dysregulation in FRDA. Here, we investigate whether sphingolipid-metabolizing enzymes are similarly affected and assess the therapeutic potential of targeting them. Our findings demonstrate that these enzymes are dysregulated across multiple FRDA models. Importantly, their modulation in vitro and in vivo significantly reduces mitochondrial dysfunction, enhances frataxin expression, and improves key pathological features of the disease, highlighting sphingolipid metabolism as a promising therapeutic target for FRDA.

Limiting intestinal iron absorption rescues glial defects and extends lifespan in a Drosophila model of Friedreich ataxia

Limiting intestinal iron absorption rescues glial defects and extends lifespan in a Drosophila model of Friedreich ataxia Ema TURKI, Estelle JULLIAN, Pierre DELAMOTTE, Anne FILIPE, Laura TIXIER CARDOSO, Sandrine MIDDENDORP, Elodie MARTIN, Veronique Monnier bioRxiv 2026.06.04.730074; doi:10.64898/2026.06.04.730074 

 Reducing intestinal iron uptake, either through treatment with bathophenanthroline disulfonic acid (BPS), an extracellular iron chelator, or by gut-specific silencing of the iron transporter Malvolio, nearly doubled fly survival. BPS treatment also improved sensitivity to dietary iron, enhanced locomotor performance, fully restored normal brain size, and prevented glial alterations. Altogether, our findings identify glial cells as early and preferential targets of frataxin deficiency in an iron-dependent manner and support the in vivo relevance of intestinal iron uptake as a potential modulator of disease severity in FRDA.

Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia

Chandra S, Kwak C, Du Z ... Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia, Cell Chemical Biology, 2026; 0.  DOI: 10.1016/j.chembiol.2026.05.004

MR3 treatment modulates molecular signatures in a cell-type-dependent manner, altering pathways related to cardiac contractility in cardiomyocytes and synaptic function in sensory neurons. Mechanistically, MR3 reduces mitochondrial reactive oxygen species and restores membrane potential in FA sensory neurons via potential allosteric reshaping of Miro1 protein. We expand the chemical diversity of this scaffold by conducting ligand-based virtual screening of over 3 billion compounds and identifying previously uncharacterized Miro1 ligands with improved docking and neuroprotective capacity.

Anodal cerebellar tDCS does not alter beta oscillations or corticokinematic coherence in Friedreich’s ataxia and healthy participants

Christian Georgiev, Mathieu Bourguignon, Scott J. Mongold, Lousin Moumdjian, Pierre Cabaraux, Gilles Naeije, Anodal cerebellar tDCS does not alter beta oscillations or corticokinematic coherence in Friedreich’s ataxia and healthy participants, Clinical Neurophysiology, Volume 190, 2026, 2111961, ISSN 1388-2457, doi:10.1016/j.clinph.2026.2111961. 

Anodal ctDCS improved FA motor symptom severity without altering SM1 excitability. 

Anodal ctDCS has a therapeutic effect in FA, however, the neurophysiology of this effect is complex and requires further investigation.

New Progress Toward Public Reimbursement of SKYCLARYS™ for People Living with Friedreich Ataxia in Quebec

TORONTO, June 8, 2026 /CNW/ - Biogen Canada Inc. is pleased to announce a positive outcome from the Institut national d'excellence en santé et en services sociaux (INESSS) re-evaluation of SKYCLARYS™ (omaveloxolone), recognizing the therapeutic value of the treatment and establishing reimbursement criteria for eligible patients living with Friedreich ataxia (FA) in Quebec. This outcome represents a positive step toward public reimbursement in the province for the only approved treatment in Canada for Friedreich ataxia.

MRI end-points for clinical trials in ataxias: recommendations from the Ataxia Global Initiative MRI Biomarkers Working Group

Öz, G., Cocozza, S., Rezende, T.J.R. et al. MRI end-points for clinical trials in ataxias: recommendations from the Ataxia Global Initiative MRI Biomarkers Working Group. Nat Rev Neurol (2026). doi:10.1038/s41582-026-01218-7 

In this Consensus Statement, the Ataxia Global Initiative MRI Biomarkers Working Group critically reviews candidate MRI end-points for trials in the most common spinocerebellar ataxias (SCA1, SCA2 and SCA3) and Friedreich ataxia and provides evidence-based, disease-specific recommendations for the selection of MRI end-points for trials in these diseases.

New clinical trial for vatiquinone

May 29, 2026 PTC Therapeutics. 

Dear Friedreich's Ataxia Community - PTC Therapeutics We are excited to share that we will be initiating a new clinical trial for vatiquinone for the treatment of individuals living with Friedreich's ...

Generation of Friedreich's ataxia induced pluripotent stem cells carrying the FXN c.165 + 5G>C splicing mutation.

Yameogo P, Gerhart BJ, Sentmanat MF, Neilson A, Cui X, Verma M, Lynch DR, Napierala JS, Napierala M. Generation of Friedreich's ataxia induced pluripotent stem cells carrying the FXN c.165 + 5G>C splicing mutation. Stem Cell Res. 2026 Jun;93:103966. doi: 10.1016/j.scr.2026.103966. Epub 2026 Mar 16. PMID: 41865460.

We generated induced pluripotent stem cells from blood lymphocytes from a FRDA patient carrying the FXN c.165 + 5G > C point mutation, which interferes with canonical splicing of intron 1 of the FXN gene. These cells allow for development of therapeutic approaches that target splicing defect in FRDA.

Xavier disease (Friedreich's ataxia variant) - Symptoms, Causes, Treatment & Prevention

📅 Updated: April 2026. Xavier disease is a very rare, autosomal‑recessive neuro‑degenerative disorder that shares many clinical features with classic Friedreich’s ataxia (FA) but is caused by distinct genetic changes. The name “Xavier disease” originates from the first family in which the condition was identified (the Xavier family) and is sometimes listed in literature as FA‑variant or Friedreich‑type ataxia with atypical genotype.

Targeting competitive Fe–S regulation to treat Friedreich’s ataxia

Campos J, Ferreira J. Targeting competitive Fe–S regulation to treat Friedreich’s ataxia. Trends in Pharmacological Sciences, 2026; 0 DOI: 10.1016/j.tips.2026.04.010

Recent discoveries reveal that frataxin (FXN) and ferredoxin 2 (FDX2) competitively regulate mitochondrial iron–sulfur (Fe–S) cluster biosynthesis through their binding to the cysteine desulfurase NFS1 and the iron-sulfur cluster scaffold protein ISCU2 complex. Here, we discuss the potential of rationally designed peptide inhibitors targeting the FDX2–NFS1 interaction as a strategy to mitigate FXN deficiency and restore Fe–S cluster biosynthesis.

A phosphorylated variant of the mast/stem cell growth factor receptor KIT is upregulated in dorsal root ganglia of Friedreich ataxia

Koeppen AH, Mazurkiewicz JE, Feustel PJ, Pelech S, Sutter C, Fu Q, Lin Q. A phosphorylated variant of the mast/stem cell growth factor receptor KIT is upregulated in dorsal root ganglia of Friedreich ataxia. Histol Histopathol. 2026 May 20:25093. doi: 10.14670/HH-25-093. Epub ahead of print. PMID: 42158966. 

Friedreich ataxia (FA) causes hypoplasia of nerve cells in dorsal root ganglia (DRG). Beyond hypoplasia, however, the lesion in DRG includes disorganization and proliferation of satellite cells, formation of residual nodules, and neuronophagia. 

KIT is a proto-oncogenic protein with prominent roles in hematopoiesis including mast cell proliferation. In conclusion, proteomic analysis confirms the prominent participation of a new truncated KIT in satellite cells in the pathogenesis of FA in DRG.

Psychological resilience in patients with Friedreich ataxia: a 6-year longitudinal analysis

Ruth Eumann, Janna Krahe, Imis Dogan, Ana Sofia Costa, Jörg B Schulz, Stella A Lischewski, Kathrin Reetz; FACROSS Study Group. Psychological resilience in patients with Friedreich ataxia: a 6-year longitudinal analysis. Neurol Res Pract. 2026 May 19;8(1):40. doi: 10.1186/s42466-026-00499-z. PubMed ID: 42157313 

 Individuals with Friedreich ataxia display reduced resilience compared to healthy controls, which is associated with greater levels of depression and anxiety. Resilience remained stable over the disease course but appeared to decline during the COVID-19 pandemic, underlining the importance of strengthening resilience and mental well-being in this population.

Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich’s ataxia models

Pido-Lopez J, Moula S, Shaban E ... Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich’s ataxia models Cell Reports Medicine, 2026; 0 doi:10.1016/j.xcrm.2026.102803

 

Slowing the curve: a single-arm meta-analysis of mFARS outcomes following omaveloxolone treatment in Friedreich ataxia

Ali A, Cheema WA, Nisar F, Reyaz U, Saad M, Talha M, et al. Slowing the curve: a single-arm meta-analysis of mFARS outcomes following omaveloxolone treatment in Friedreich ataxia. BMJ Neurology Open. 2026;8:e001670. doi:10.1136/bmjno-2026-001670 

Sensitivity analyses confirmed robustness. Controlled trials demonstrate significant short-term improvement with omaveloxolone, while real-world data show consistent progression at rates substantially slower than natural history. These complementary findings support a disease-modifying effect of omaveloxolone in FRDA.

Swinburne researcher discovers broccoli extract could halt incurable neurological disorder

Newscorp Australia. May 19, 2026.

Associate Professor Faith Kwa leads the Drug Discovery for Chronic Diseases Laboratory at Swinburne University of Technology. Her research focuses on finding new treatments for Friedreich ataxia, a rare inherited genetic condition that currently has no cure. Friedreich ataxia affects around 260 people in Australia and can have devastating consequences.

The next step for Associate Professor Kwa’s team is to secure funding for a clinical trial. The trial would test sulforaphane in patients and determine the most effective doses for treating the condition. This critical clinical study could demonstrate that a compound derived from a common vegetable might help tackle one of the world’s rarest and most challenging diseases – showing that groundbreaking medical discoveries can begin in the most unexpected places. 

Crucially, SF can cross the blood–brain barrier, an advantage lacking in many drugs under investigation for neurodegenerative diseases like Friedreich ataxia (FRDA). FRDA is an inherited, incurable and debilitating condition caused by low levels of a protein known as frataxin. Our laboratory showed that clinically relevant doses of SF not only improve survival of spinal cord cells generated from stem cells taken from FRDA individuals but also increase frataxin levels. 

At approximately $5000 per patient per year, SF is more affordable than the only approved treatment, which costs hundreds of thousands of dollars annually. Sulforaphane exemplifies a future therapy that is sustainable, safe, and accessible to people.

New RESTORE-FA results show DT-216P2 improved balance and fatigue within 4 weeks, with tolerable safety.

NeurologyLive®. May 19, 2026. DT-216P2 Shows Dose-Dependent Frataxin Increases and Clinical Improvements After 4 Weeks of IV Dosing in Friedreich Ataxia.Design Therapeutics has reported positive 4-week biomarker and clinical data from the ongoing phase 1/2 RESTORE-FA clinical trial evaluating DT-216P2, an investigational small-molecule GeneTAC therapy designed to increase endogenous frataxin (FXN) expression by targeting the GAA trinucleotide repeat expansion in the FXN gene—the underlying genetic cause of Friedreich ataxia (FA). 

The data showed dose-dependent increases in FXN mRNA and protein alongside improvements across multiple clinical outcome measures in patients treated with weekly intravenous dosing over 4 weeks.We observed both dose-dependent increases in FXN levels and dose-dependent improvements across multiple clinical measures, including mFARS, upright stability score and patient-reported fatigue.

Based on these findings, we believe DT-216P2 has the potential to be a best-in-disease treatment for patients with FA and look forward to advancing the program toward registrational development.”