Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis

Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis Marnie L Maddock, Sara Miellet, Anjila Dongol, Amy J Hulme, Chloe K Kennedy, Louise A Corben, Rocio K Finol-Urdaneta, Alberto Nettel-Aguirre, Chiara Dionsi, Martin B Delatycki, Joel M Gottesfeld, Massimo Pandolfo, Elisabetta Soragni, Sanjay I Bidichandani, Jarmon G Lees, Shiang Y Lim, Jill S Napierala, Marek Napierala, Mirella Dottori bioRxiv 2026.03.18.712785; doi: 10.64898/2026.03.18.712785 

Together, these findings implicate cell type specific transcriptional programs as potential drivers of selective vulnerability and establish a framework for prioritising biomarkers in FRDA.

The multifaceted nature of Friedreich ataxia: strategies for comprehensive patient care.

Raza, M. L., Rawalia, M. A., Fatima, Z., & Zehra, H. (2026). The multifaceted nature of Friedreich ataxia: strategies for comprehensive patient care. Neurodegenerative Disease Management, 1–9. doi:10.1080/17582024.2026.2645501

Design Therapeutics Maps H2 Data Readouts for RESTORE-FA

MarketBeat. Sun, March 15, 2026. RESTORE-FA targets a demonstrable increase in endogenous frataxin (measured in mRNA and protein, including muscle biopsy) after 12 weeks of dosing, with topline data expected in the second half of the year. According to Shah, achieving that type of increase would be notable because it has “never been achieved before.” He said the company is measuring both frataxin mRNA and frataxin protein, describing mRNA as “completely endogenous” and specifying that the assay looks at “normal processed mRNA.” Measurements will be taken in whole blood cells and also in affected tissue via muscle biopsy, though he noted biopsy sampling is limited and would generally be conducted before and after dosing, with a possible third sample.

On the question of GeneTAC selectivity, Shah pointed to preclinical work across multiple FA patient-derived cell types. He said GeneTAC molecules increased endogenous frataxin RNA and led to downstream effects including normalization of protein levels and improvements in functions such as cis-aconitate and cellular respiration. He added that exposure of wild-type genotype cells to an FA GeneTAC molecule had no impact because the repeat number in the wild-type allele is short and therefore does not produce a functional consequence when treated.

Patient population and endpoints in the FA study Shah described RESTORE-FA enrollment criteria as “pretty permissive” beyond genetic confirmation of FA, including ambulatory and wheelchair-bound patients. He said the current study explores both IV and subcutaneous (sub-Q) administration to help determine dose route, dosing interval, and the frataxin response to inform future clinical investigation. While functional assessments are customary in FA trials and are being performed, he said the primary goal of the study is to look for a frataxin response.

Biallelic Truncating DNAH14 Variant in Siblings with Neurodevelopmental Disorder and Predominant Ataxia: Clinical Report and Literature Review

Baris S, Dogan M, Terali K, Gezdirici A, Eroz R, Yucel PP, Kilic H, Yavas C, Yildirim G, Baris I. Biallelic Truncating DNAH14 Variant in Siblings with Neurodevelopmental Disorder and Predominant Ataxia: Clinical Report and Literature Review. Int J Mol Sci. 2026 Jan 6;27(2):575. doi: 10.3390/ijms27020575. PMID: 41596228; PMCID: PMC12841059.

The coexistence of FRDA expansions and a truncating DNAH14 variant suggests a potential dual genetic contribution to the observed phenotype, in which FRDA-associated pathology likely underlies the ataxia, while DNAH14 disruption may contribute to additional neurodevelopmental features. This is the first report describing the co-occurrence of FRDA and a homozygous truncating DNAH14 variant in the same individuals, broadening our understanding of overlapping neurogenetic mechanisms. Our findings expand the phenotypic spectrum of DNAH14-related disorders and highlight the importance of considering multilocus pathogenic variants in patients with complex or atypical ataxia presentations.

Hereditary Ataxias: From Pathogenesis and Clinical Features to Neuroimaging, Fluid, and Digital Biomarkers-A Scoping Review

Bernardi E, López-Lombardía Ó, Olmedo-Saura G, Pagonabarraga J, Kulisevsky J, Pérez-Pérez J. Hereditary Ataxias: From Pathogenesis and Clinical Features to Neuroimaging, Fluid, and Digital Biomarkers-A Scoping Review. Int J Mol Sci. 2026 Jan 15;27(2):881. doi: 10.3390/ijms27020881. PMID: 41596528; PMCID: PMC12841259.

We conducted a scoping review of PubMed and complementary sources (2010-2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich's ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). 

 Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias.

Quantifying Placebo Effects in Hereditary Ataxia Trials: A Meta-Analysis of Scale for the Assessment and Rating of Ataxia (SARA) Score Changes

Petit E, Beaubois-Gandoin A, Durr A, du Montcel ST, Coarelli G. Quantifying Placebo Effects in Hereditary Ataxia Trials: A Meta-Analysis of Scale for the Assessment and Rating of Ataxia (SARA) Score Changes. Mov Disord. 2026 Jan 29. doi: 10.1002/mds.70151. Epub ahead of print. PMID: 41612637. 

 The analysis indicates a measurable placebo effect on SARA scores. Both intervention type and geographic region significantly influenced the strength of this effect, suggesting roles for patient expectations and cultural factors. Additionally, there was a trend toward reduction of placebo response as trial duration increased.

Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis

Pazos-Gil M, Medina-Carbonero M, Sanz-Alcázar A, Portillo-Carrasquer M, Oliveira-Jorge L, Hernández G, Sánchez M, Delaspre F, Cabiscol E, Ros J, Tamarit J. Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis. iScience. 2026 Jan 5;29(2):114625. doi: 10.1016/j.isci.2025.114625. PMID: 41623463; PMCID: PMC12857413.

In this study, we have analyzed iron homeostasis in a mouse model presenting pathological frataxin deficiency (FXNI151F). Our results reveal tissue-specific alterations of iron regulatory proteins (IRPs).

Friedreich-Ataxie: Die häufigste autosomal-rezessiv vererbte Ataxie [Friedreich's ataxia: The most common autosomal recessive inherited ataxia]

Erdlenbruch F. Friedreich-Ataxie: Die häufigste autosomal-rezessiv vererbte Ataxie [Friedreich's ataxia: The most common autosomal recessive inherited ataxia]. MMW Fortschr Med. 2026 Feb;168(Suppl 1):40-42. German. doi: 10.1007/s15006-026-5619-2. PMID: 41699226.

Die Friedreich-Ataxie ist eine seltene, autosomal-rezessiv vererbte, (neuro)degenerative Multisystemerkrankung. Neben dem Nervensystem sind auch das Herz, der Bewegungsapparat und der Stoffwechsel beeinträchtigt. Die Krankheit bricht i. d. R. im Jugendalter aus. …

Coexistence of Friedreich's Ataxia and Esophageal Cancer: A Case Report

Mehrban A, Babamahmoodi A, Hamidian MT, Amiri B, Ramzani P, Karimi M. Coexistence of Friedreich's Ataxia and Esophageal Cancer: A Case Report. Clin Case Rep. 2026 Feb 24;14(3):e72153. doi: 10.1002/ccr3.72153. PMID: 41756699; PMCID: PMC12932118.

Friedreich's ataxia (FA) is a rare autosomal recessive neurodegenerative disorder. Although FA is frequently associated with cardiomyopathy and diabetes mellitus, its coexistence with solid malignancies is exceptionally rare. To date, only a limited number of gastrointestinal cancers have been reported in patients with FA.

Therapeutic Potential of Deferiprone-Resveratrol Hybrid (DFP-RVT) Against Hepatic Iron Overload in β-Thalassemia Mice: A Proteomic Analysis

Maneekesorn S, Yingchutrakul Y, Simanon N, Kumsab J, Butkinaree C, Moonmuang S, Li J, Charoenkwan P, Koonyosying P, Paradee N, Srichairatanakool S, Chuljerm H. Therapeutic Potential of Deferiprone-Resveratrol Hybrid (DFP-RVT) Against Hepatic Iron Overload in β-Thalassemia Mice: A Proteomic Analysis. Biomolecules. 2026 Feb 23;16(2):338. doi: 10.3390/biom16020338. PMID: 41750406; PMCID: PMC12937802. 

Proteomic analysis was performed on liver tissues from baseline control, iron-overloaded, and DFP-RVT-treated mice to identify differentially expressed proteins and affected pathways. Iron overload resulted in marked downregulation of mitochondrial proteins, particularly components of oxidative phosphorylation and iron-sulfur cluster-associated pathways, including frataxin.

Our findings suggest that frataxin may be a key determinant of mitochondrial integrity and function in the context of hepatic iron overload. The observed frataxin loss in IO mice, likely driven by iron toxicity, contributes to hepatocellular damage. Importantly, DFP-RVT treatment restored frataxin expression, which may account for the recovery of mitochondrial protein levels and overall mitochondrial function

Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders

de Oliveira MR. Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders. Front Pharmacol. 2026 Feb 12;17:1748360. doi: 10.3389/fphar.2026.1748360. PMID: 41769702; PMCID: PMC12935978.

In conclusion, DMF exerts multifaceted and cell type-specific actions on mitochondria. Understanding these mechanisms may guide optimized therapeutic strategies and the identification of biomarkers for precision use in neurological disorders.

An Exploration of Vitamin D Deficiency and Clinical Status in Friedreich's Ataxia Patients in the UK

Fleszar Z, Thomas-Black G, Garcia-Moreno H, Cook A, Giunti P. An Exploration of Vitamin D Deficiency and Clinical Status in Friedreich's Ataxia Patients in the UK. Mov Disord Clin Pract. 2026 Mar 6. doi: 10.1002/mdc3.70529. Epub ahead of print. PMID: 41789678. 

Given the established benefits for bone health, particularly in a cohort in which falls are highly prevalent, coupled with the low cost and good safety profile of supplementation, we recommend that vitamin D deficiency should be screened for and actively managed in all FRDA patients.

Identification of Biological Subtypes of Friedreich Ataxia with Structural MRI-based Machine Learning

Pontillo G, Penna S, Arrigoni F, Bender B, Boesch S, Brunetti A, Cendes F, Chopra S, Corben LA, Deistung A, Delatycki MB, Diciotti S, Dogan I, Egan GF, França MC Jr, Georgiou-Karistianis N, Göricke SL, Henry PG, Hernandez-Castillo CR, Hutter D, Joers JM, Lenglet C, Lindig T, Lodi R, Manners DN, Martinez ARM, Martinuzzi A, Marzi C, Mascalchi M, Nachbauer W, Pane C, Peruzzo D, Pishardy PK, Reetz K, Rezende TJR, Romanzetti S, Saccà F, Schoels L, Schulz JB, Stefani A, Synofzik M, Thomopoulos SI, Thompson PM, Timmann D, Tonon C, Vavla M, Harding IH, Cocozza S. Identification of Biological Subtypes of Friedreich Ataxia with Structural MRI-based Machine Learning. Radiology. 2026 Mar;318(3):e251386. doi: 10.1148/radiol.251386. PMID: 41805414. 

Using the SuStaIn algorithm, three distinct structural MRI-based subtypes of FRDA were identified, with different patterns of brain degeneration and associations with clinical severity

22463 - MEJORÍA EN ESCALAS CLÍNICAS DE ATAXIA DE FRIEDREICH EN TRATAMIENTO CON OMAVELOXOLONA: A PROPÓSITO DE UN CASO

N. Rodríguez Albacete, A. Horga Hernández, A. Guerrero Sola, L. Galán Dávila,, 22463 - MEJORÍA EN ESCALAS CLÍNICAS DE ATAXIA DE FRIEDREICH EN TRATAMIENTO CON OMAVELOXOLONA: A PROPÓSITO DE UN CASO, Neurology Perspectives, Volume 5, Supplement 1, 2025, 111558, ISSN 2667-0496, doi:10.1016/S2667-0496(26)00777-5. 

En este caso, omaveloxolona se asoció a una mejoría clínica en escalas estandarizadas en una paciente con AF. Estos hallazgos contribuyen a incrementar la experiencia en práctica clínica real con este fármaco, aunque se requerirán mayor número de pacientes y seguimiento a largo plazo para confirmar estos resultados.

22211 - ANÁLISIS DE BIOMARCADORES PREDICTORES DE LA PROGRESIÓN EN LA ATAXIA DE FRIEDREICH (FRDA)

L. Manrique Arregui, F. Martínez Dubarbie, A. Pelayo Negro, N. Benítez Calle, M. Sánchez Peláez, D. Cota González, R. Martínez Díaz, I. Sánchez, A. Matilla, J. Infante Ceberio,, 22211 - ANÁLISIS DE BIOMARCADORES PREDICTORES DE LA PROGRESIÓN EN LA ATAXIA DE FRIEDREICH (FRDA), Neurology Perspectives, Volume 5, Supplement 1, 2025, 110789,ISSN 2667-0496, doi:10.1016/S2667-0496(26)00008-6.

Los pa4cientes con FDRA presentan mayores niveles de NfL en LCR y menor expresión de FXN. Aunque GAA1, DB y FXN se asociaron con la gravedad del fenotipo, GAA1 y SARA basal fueron los principales factores de progresión. Los NfL en LCR no se asociaron con la gravedad ni con la progresión clínica.

P602: FXN repeat-primed PCR and long-read sequencing reveal non-canonical repeat expansions,

P602: FXN repeat-primed PCR and long-read sequencing reveal non-canonical repeat expansions, Obadia, Benjamin et al. Genetics in Medicine Open, Volume 4, 104093; DOI: 10.1016/j.gimo.2026.104093 

This study validated the CE-based assay as an efficient and accurate screening method for detecting repeat expansions in FXN. PacBio sequencing revealed that GAA interruptions were present primarily in alleles below 200 repeats in our cohort. Identifying these interruptions may have significant clinical relevance; however, additional larger scale studies and an interpretation paradigm will be needed prior to incorporating interruption data into routine testing.

An exploration of barriers to diagnosis in Friedreich's ataxia

P270: An exploration of barriers to diagnosis in Friedreich's ataxia. Madden, Anna et al.; Genetics in Medicine Open, Volume 4, 103764. doi:10.1016/j.gimo.2026.103764 

Diagnostic delay remains common in FA, with an average delay of over four years between symptom onset and diagnosis. Misdiagnoses, clinician dismissal of symptoms, and genetic testing barriers remain the top three reported barriers among this patient population. These findings highlight key areas for improvement in both clinical recognition and appropriate genetic testing strategies in FA. Targeting efforts that increase awareness of FA signs, symptoms, and appropriate genetic testing with neurologists and geneticists, who are the most common diagnosing providers, may help to reduce diagnostic delay.

Economic Issues and Viability of Gene-Based Molecular Therapies for Cardiovascular Disease

Economic Issues and Viability of Gene-Based Molecular Therapies for Cardiovascular Disease; Hlávka, Jakub, Canadian Journal of Cardiology, Volume 0, Issue 0. doi:10.1016/j.cjca.2026.03.004 

The economic viability of cardiovascular GMTs will therefore hinge on whether their scientific potential can be translated into payment and evaluation frameworks that are compatible with health system budget constraints. This will require coordinated approaches that move beyond traditional single-payer decisions, including alternative payment models that better align upfront costs with verified, durable outcomes, and closer alignment between regulators, health technology assessment bodies, and payers on standards for long-term evidence generation. Without such coordination, particularly under stringent cost-effectiveness requirements applied to large cardiovascular populations, these therapies are likely to remain clinically promising yet economically difficult to integrate into routine care.

Nerve Ultrasound in Patients With Friedreich Ataxia

Kneer K, Stahl JH, Winter N, Wittlinger J, Männlin S, Gasimli T, Schöls L, Fleszar Z, Hayer S, Grimm A. Nerve Ultrasound in Patients With Friedreich Ataxia. Muscle Nerve. 2026 Mar;73(3):395-402. doi: 10.1002/mus.70091. Epub 2025 Dec 4. PMID: 41340583; PMCID: PMC12888831.

Peripheral nerve morphology in FRDA is variable and includes not only nerve enlargement but also nerve atrophy, thus reflecting complex segmental pathology beyond axonal degeneration.

Dual therapy with monoamine oxidase A inhibition and Nrf2 activation improves autonomic nervous system and cardiac function in a mouse model of Friedreich’s ataxia

BPS2026 – Dual therapy with monoamine oxidase A inhibition and Nrf2 activation improves autonomic nervous system and cardiac function in a mouse model of Friedreich’s ataxia. Figueroa, Francisco et al.; Biophysical Journal, Volume 125, Issue 4, 398a - 399a. doi:10.1016/j.bpj.2025.11.2441 

These findings identify SR-localized sympathetic signaling defects as a novel mechanism for arrhythmia in FA hearts. Dual targeting of MAO-A and Nrf2 provides complementary benefits, with clorgyline improving ANS and OMAV driving antioxidant defense, altogether restoring cardiac conduction and function.

Myo-inositol elevation as an in vivo marker of reactive gliosis in pediatric Friedreich Ataxia: evidence from HERMES-edited MR spectroscopy

William Gaetz, Muhammad G. Saleh, Charlotte Birnbaum, Luke Bloy, Timothy P.L. Roberts, David R. Lynch, Myo-inositol elevation as an in vivo marker of reactive gliosis in pediatric Friedreich Ataxia: evidence from HERMES-edited MR spectroscopy, NeuroImage: Clinical, 2026, 103983, ISSN 2213-1582, doi:10.1016/j.nicl.2026.103983. 

These findings support a model of early reactive gliosis in pediatric FRDA, indexed by elevated mI and occurring without statistically significant neuronal loss, (acknowledging that significant reductions in tNAA may require larger samples to resolve), and extend prior cerebellar-focused work to the primary motor cortex. While GSH and GABA + did not differ between groups, the observed mI elevations highlight myo-inositol as a practical in vivo biomarker of astrocytic activation and a candidate marker for disease progression in FRDA. Longitudinal studies are needed to confirm its sensitivity to clinical trajectory and therapeutic response.

The Scottish Medicines Consortium (SMC), which advises on newly licensed medicines for use by NHSScotland, has today (Monday, March 9) published advice on five medicines.

Published : March 09, 2026​. 

Omaveloxolone (Skyclarys®) was not recommended for the treatment of patients aged 16 years and older with Friedreich’s ataxia, a rare inherited condition that causes damage to the nervous system.

he committee was unable to accept omaveloxolone for the treatment of Friedreich’s ataxia. The company’s evidence around the cost effectiveness of the treatment was not sufficient.

Design Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Recent Business Updates

CARLSBAD, Calif., March 09, 2026 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. (Nasdaq: DSGN), a clinical-stage biotechnology company developing treatments for serious degenerative genetic diseases, today reported fourth quarter and full year 2025 financial results and highlighted business updates and upcoming milestones across its GeneTAC® portfolio. 

Friedreich Ataxia (FA): Design continues to dose FA patients in its RESTORE-FA Phase 1/2 MAD trial and anticipates providing an update on the effect of DT-216P2 on endogenous frataxin levels following 12 weeks of dosing in the second half of 2026.

Voyager Reports Fourth Quarter and Full Year 2025 Financial and Operating Results

March 09, 2026 16:01 ET | Source: Voyager Therapeutics, Inc.​. 

Neurocrine partnership update: Neurocrine has stated that, pending successful FDA IND clearance, it intends to initiate a clinical trial with NBIB-‘223 for Friedreich’s ataxia in H2 2026.

PLong-term use of omaveloxolone in patients with Friedreich ataxia: up to 5 years of natural history propensity score matching from the MOXIe OLE

234PLong-term use of omaveloxolone in patients with Friedreich ataxia: up to 5 years of natural history propensity score matching from the MOXIe OLE Nachbauer, W., D. Lynch et al. Neuromuscular Disorders, Volume 53, 106043 doi:10.1016/j.nmd.2025.106043 

 Updated safety analyses will also be presented. Continued analysis of the MOXIe OLE data informs on long-term efficacy and safety of omaveloxolone in patients with FA and provides relevant insights regarding disease progression in patients treated with omaveloxolone relative to the natural pattern of FA progression in the FACOMS cohort.

An Open-Label, Single Dose Study to Assess the Breast Milk Pharmacokinetics of Omaveloxolone in Healthy Lactating Women

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026​. Poster Number: 316 T. An Open-Label, Single Dose Study to Assess the Breast Milk Pharmacokinetics of Omaveloxolone in Healthy Lactating Women. Hamim Zahir, PhD, Biogen, Inc., Lucy Wu, PhD, Biogen, Inc., Susie Sinks, Biogen, Inc., Andre Arizpe, PharmD, Biogen, Inc., Sarah Chambers Gurson, Biogen, Inc., Konstantine Skordos, Biogen, Inc.

Objective: To determine the relative estimated infant exposure of omaveloxolone through breast milk following a single dose of 150 mg in healthy lactating women.

Conclusions: The results indicate that after oral administration of a single dose of 150 mg omaveloxolone, breast milk–fed infants may be exposed to a small fraction.(<1%) of the adult dose. The safety findings observed in this study are consistent with the known safety profile for omaveloxolone.

Diagnoses and Procedures Observed Prior to Friedreich Ataxia Diagnosis: A Real-World US Medical Claims Analysis

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Poster Number: 291 T. Diagnoses and Procedures Observed Prior to Friedreich Ataxia Diagnosis: A Real-World US Medical Claims Analysis. Alicia Henriquez, MD, Seattle Children's Hospital, Meredith Hatcher, Texas Movement Disorder Specialists, Georgetown, TX, USA, Sarah Doss, University of Nebraska Medical Center, Omaha, NE, USA, Partha S. Ghosh, MD, Boston Children's Hospital, Pravin Khemani, MD, Swedish Neuroscience Institute, Seattle, WA, USA, Sarah M. England, PhD, Biogen, Inc., Queeny Ip, Komodo Health, Xinshuo Ma, Komodo Health, Saila Chen, Komodo Health, Robin Avila, PhD, Biogen, Alexandra DiDonato, PharmD, Biogen. 

Objective: To characterize diagnoses and procedures received by patients prior to diagnosis of FA. 

Conclusions: Medical claims data enhance our understanding of the clinical journey of patients leading to FA diagnosis. Prior to FA diagnosis, patients encounter various healthcare professionals, receive a variety of diagnoses, and experience a multitude of procedures, which may lead to delayed time to definitive FA diagnosis. Expediting the diagnostic pathway for FA through timely referrals enables earlier intervention, which is imperative for reducing disease burden and enhancing patient quality of life.

High prevalence of pathogenic expanded composite repeats in Friedreich ataxia: Need for a more accurate diagnostic testing strategy

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026​. Poster Number: 295 T. High prevalence of pathogenic expanded composite repeats in Friedreich ataxia: Need for a more accurate diagnostic testing strategy. Sanjay Bidichandani, MBBS, PhD, University of Oklahoma, Morgan Devore, MS, University of Oklahoma, Christina Lam, BS, University of Oklahoma, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. High prevalence of pathogenic expanded composite repeats in Friedreich ataxia: Need for a more accurate diagnostic testing strategy. 

Objectives: To determine the true prevalence and variety of pathogenic composite alleles in FRDA by characterizing the precise sequence of the expanded alleles in a large prospective series of patients. To overcome the expense and unwieldy nature of whole genome longread sequencing by developing a robust, logistically-feasible, and cost-effective testing strategy to accurately detect and characterize these missing pathogenic alleles in FRDA.

US Medical Claims Database of Patients With Friedreich Ataxia Prescribed Omaveloxolone: Clinical Events From Diagnosis to Initiation of Treatment

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Poster Number: 296 T. US Medical Claims Database of Patients With Friedreich Ataxia Prescribed Omaveloxolone: Clinical Events From Diagnosis to Initiation of Treatment. Sheng-Han Kuo, PhD, Columbia University Medical Center, New York, NY, USA, Liana S. Rosenthal, MD, PhD, Johns Hopkins University School of Medicine, Boyang Bian, PhD, Biogen, Inc., Alexandra DiDonato, PharmD, Biogen, Sarah M. England, PhD, Biogen, Inc., Daniel Gomes, Voxanalytica, Nicholas D’Alberto, Biogen, Inc., James McKay, PhD, Biogen, Inc., Tony Wang, PhD, Voxanalytica, Robin Avila, PhD, Biogen. 

Objective: To describe clinical events and patient profiles in individuals with FA prior to omaveloxolone initiation using US medical claims.

Conclusions: These findings highlight that patients with FA experienced progressive worsening of symptoms, including bulbar, respiratory, and mobility impairments, between initial diagnosis and initiation of omaveloxolone. This underscores the importance of identifying decision points that should prompt earlier treatment intervention.

Long-Term Safety and Tolerability of Omaveloxolone in Patients With Friedreich Ataxia: Up to 6-Year Data From the MOXIe Open-Label Extension

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026​.Poster Number: 298 T. Long-Term Safety and Tolerability of Omaveloxolone in Patients With Friedreich Ataxia: Up to 6-Year Data From the MOXIe Open-Label Extension. Theresa Zesiewicz, MD, MD, University of South Florida Ataxia Research Center, Tampa, Florida, USA, Susan Perlman, MD, University of California, Los Angeles, Martin B. Delatycki, Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, J. Chad Hoyle, Ohio State University College of Medicine, Sylvia Boesch, MD, Medical University of Innsbruck, Wolfgang Nachbauer, MD, PhD, Medical University of Innsbruck, Paola Giunti, MD, PhD, University College Hospital, George Wilmot, MD, PhD, Emory University School of Medicine, SH Subramony, MD, University of Florida Health, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Syed Farooq, Biogen International GmbH, Shobhana Natarajan, PhD, Biogen, Inc., Rose M. Domingo-Horne, MD, Biogen, Inc., Andre Arizpe, PharmD, Biogen, Inc., Jonathan Smith, MSc, Biogen Idec Ltd, Nicolas Folschweiller, Biogen, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 

Objective: To evaluate the long-term safety and tolerability of omaveloxolone treatment in the MOXIe OLE.Conclusions: This updated analysis of the MOXIe OLE provides up to 6 years of continuous long-term safety and tolerability data regarding omaveloxolone use in patients with FA. 

Safety findings were consistent with the previously known safety profile.

Assessing Real-World Experiences on SKYCLARYS® (Omaveloxolone) (ARIES) in Patients With Friedreich Ataxia: An Observational Study

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026​. Poster Number: 292 T. Assessing Real-World Experiences on SKYCLARYS® (Omaveloxolone) (ARIES) in Patients With Friedreich Ataxia: An Observational Study. Elissa Hult, Biogen, Inc., Sarah M. England, PhD, Biogen, Inc., Boyang Bian, PhD, Biogen, Inc., James McKay, PhD, Biogen, Inc., Tami Sova, Biogen, Inc., Molly Scannell Bryan, PicnicHealth, Robin Avila, PhD, Biogen. 

Objective: To understand omaveloxolone treatment experience through PROs, the associated longitudinal clinical outcomes, and HCRU in the US real-world setting. 

Conclusions: This currently enrolling study will provide a means to longitudinally follow patients with FA treated with omaveloxolone in real-world clinical practice without the need for clinical sites. The findings will increase understanding of the real-world experience with omaveloxolone use in patients underrepresented in clinical trials and the impact on long-term patient experience and outcomes.

Interim Analysis of mFARS Trajectories Across 5 Years in the MOXIe Extension: Impact of Omaveloxolone Initiation Timing in Friedreich Ataxia

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026, Poster Number: 297 T. Interim Analysis of mFARS Trajectories Across 5 Years in the MOXIe Extension: Impact of Omaveloxolone Initiation Timing in Friedreich Ataxia. Theresa Zesiewicz, MD, MD, University of South Florida Ataxia Research Center, Tampa, Florida, USA, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA, Claudia Yang Santos, PhD, Biogen, Inc., Susie Sinks, Biogen, Inc., Syed Farooq, Biogen International GmbH, Jonathan Smith, MSc, Biogen Idec Ltd, Shobhana Natarajan, PhD, Biogen, Inc., Nicolas Folschweiller, Biogen. 

Objective: Compare mFARS score trajectories between patients who initially received omaveloxolone in MOXIe Part 2 and patients who started omaveloxolone 1 year later in the OLE. 

Conclusions: The omaveloxolone-omaveloxolone group that started treatment 1 year before the placebo-omaveloxolone group showed numerically slower mFARS progression, relatively. Nevertheless, all patients receiving omaveloxolone experienced sustained benefit in slowing of mFARS decline throughout the analysis period.

Efficacy and Safety of a Novel Investigational AAV FXN Gene Therapy (SGT-212) for the Treatment of Friedreich’s Ataxia

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026​. Poster Number: 299 T. Efficacy and Safety of a Novel Investigational AAV FXN Gene Therapy (SGT-212) for the Treatment of Friedreich’s Ataxia. Matthew Harmelink, MD, Solid Biosciences, Brandon Chan, PhD, Solid Biosciences, Jun Lee, PhD, Solid Biosciences, Jessica Boehler, PhD, Solid Biosciences, Jamie Marshall, PhD, Solid Biosciences, Gourav Choudhury, PhD, DABT, Franklin Labs, Heather Born, PhD, GEMMA Biotherapeutics, Juliette Hordeaux, DVM, PhD, DECVP, GemmaBio, James Wilson, MD, PhD, GemmaBio, Jessie Hanrahan, PhD, Solid Biosciences, Gabriel Brooks, MD, Solid Biosciences, Nicholas Christoforou, PhD, Solid Biosciences. 

Approach: SGT-212, Solid Biosciences’ investigational AAV gene therapy for FA, expresses full-length, human FXN under a ubiquitous promoter. Preclinical evaluation of SGT-212 assessed neurologic and cardiac outcomes in conditional Fxn knockout mouse models targeting the nervous system (nKO) and heart (cKO). Long-term safety and biodistribution were assessed in non-human primates (NHPs) to support a first-in-human clinical trial using a dual route of administration via intraparenchymal dentate nucleus (IDN) and intravenous (IV) infusions. This multisystem, dual route approach was designed to target the neurologic, cardiac and systemic manifestations of FA.

Conclusions: These nonclinical studies demonstrate that a one-time administration of SGT-212 increases FXN expression in disease-relevant tissues, improves neurologic and cardiac phenotypes in mouse models, and is well tolerated in NHPs. Altogether, this positive, nonclinical data package supports the Phase 1b FALCON trial (NCT07180355), a first-in-human evaluation of SGT-212, which is actively screening participants.

Interim observations from a long-term open label study evaluating daily nomlabofusp administration in patients with Friedreich’s ataxia

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Poster Number: 419 O. Russell Clayton, DO, Larimar Therapeutics Inc., Erin Coyle, Larimar Therapeutics Inc., Flavia De Toni, PhD, Larimar Therapeutics Inc., Mohamed Hamdani, Larimar Therapeutics Inc. 

Objective: Evaluate interim observations related to FXN levels, clinical measures, and safety in patients with FA receiving long term administration of nomlabofusp. 

Conclusion: In patients with FA, daily administration of nomlabofusp for 6 months resulted in increased skin FXN to levels that were within the range expected in asymptomatic carriers with no phenotypic expression of disease. After 1 year of nomlabofusp treatment, values from clinical measures trended lower, suggesting a potential for clinical improvement in the context of increased FXN levels. There is a risk of anaphylaxis during early treatment, particularly in patients who had past exposure to nomlabofusp. Long term treatment with nomlabofusp appeared to be well tolerated.

Unmet Needs of Individuals With Friedreich Ataxia Cardiomyopathy: Insights From the Lexeo Friedreich Ataxia Cardiac Advisory Council

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Poster Number: 293 T. Cardiomyopathy: Insights From the Lexeo Friedreich Ataxia Cardiac Advisory Council. Joslyn Crowe, MSW, MA, Lexeo Therapeutics, Aly Bourbeau, Lexeo FA Cardiac Advisory Council, Marc Likins, Lexeo FA Cardiac Advisory Council, Amalia Maranhao, Lexeo FA Cardiac Advisory Council, Madelyn Raynsford, Lexeo FA Cardiac Advisory Council, Nilomi Shah, PharmD, Lexeo Therapeutics. 

 The FA Cardiac Advisory Council meeting aimed to understand crucial gaps and shared goals related to heart health, entry points in cardiac care and diagnostic challenges. A pre-meeting survey was completed by 10 council members. 

 Conclusions: The FA Cardiac Advisory Council identified key collaborative opportunities to increase knowledge around FA-CM and improve cardiac care by: sharing insights and stories on their lived experiences with FA-CM, developing materials to better inform newly diagnosed individuals with FA, building a community for those impacted by FA-CM via digital and social media channels, and providing on clinical trial experience.

Dexterity Outcomes in Friedreich Ataxia as Measured by mFARS and FA-ADL

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Poster Number: 294 T. Dexterity Outcomes in Friedreich Ataxia as Measured by mFARS and FA-ADL. Sheng-Han Kuo, PhD, Columbia University Medical Center, New York, NY, USA, Syed Farooq, Biogen International GmbH, Claudia Yang Santos, PhD, Biogen, Inc., Shobhana Natarajan, PhD, Biogen, Inc., Jonathan Smith, MSc, Biogen Idec Ltd, Richard Lawson, MSc, Biogen. 

Objective: To assess the impact of Friedreich ataxia (FA) on the activities of daily living associated with dexterity at different levels of disease severity.

Conclusions: Dexterity outcomes measured by FA-ADL have a strong association with mFARS score, suggesting that mFARS can also capture dexterity progression in FA.

Patient-reported experiences during long-term omaveloxolone treatment in Friedreich ataxia: survey design and planned qualitative analysis

MDA Clinic & Scientific Conference 2026. March 8 – 11, 2026. Patient-reported experiences during long-term omaveloxolone treatment in Friedreich ataxia: survey design and planned qualitative analysis. Susan Perlman, MD, University of California, Los Angeles, Theresa Zesiewicz, MD, MD, University of South Florida, Matthew Lafleur, MA, Bionews, Inc., Pensacola, FL, USA, Libby Schwers, BA, With Love, Libby, Des Moines, Iowa, USA, Jennifer Farmer, MS, Friedreich's Ataxia Research Alliance, Pearl WU, MS, Biogen, Claudia Yang Santos, PhD, Biogen, Inc., Kyle Fowler, MBiolSci, Syneos Health Consulting, Zurich, Switzerland, Fiona Thomas, MBChB, Syneos Health Consulting, London, UK, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 

This qualitative survey will explore patient-reported lived experiences and perceptions of functional outcomes among adults (≥18 years) with Friedreich Ataxia (FA) receiving long-term omaveloxolone treatment in the United States.

Health care, social, educational, and employment needs of individuals affected by rare diseases and their families in Catalonia, Spain

Calmaestra-Carrillo, E., Vernet, R., Torrent-Farnell, J. et al. Health care, social, educational, and employment needs of individuals affected by rare diseases and their families in Catalonia, Spain. Orphanet J Rare Dis (2026). doi:10.1186/s13023-026-04281-x 

This study aims to describe the perceived needs of individuals affected by rare diseases and their families, regarding healthcare, social, educational, and employment systems.

FDA reversals leave investors worrying about the fates of other experimental drugs

Published Fri, Mar 6 2026. The FDA in the past year has denied or discouraged applications of at least eight new drugs, according to RTW Investments. 

The agency initially refused to review Moderna’s flu shot before reversing course. Companies have accused the FDA of reversing previous guidance, leaving investors worried about the prospects for other drugs in the pipeline. 

FDA Commissioner Marty Makary and other leaders have publicly pledged flexibility for drugs treating rare diseases. Investors don’t feel like recent moves reflect that.