Physiologically Regulated Frataxin Gene Replacement Restores Neurological Function in a Mouse Model of Friedreich Ataxia

Pilotto F, Dall'Agnol L, Reutenauer L, Paschaki M, Puccio H. Physiologically Regulated Frataxin Gene Replacement Restores Neurological Function in a Mouse Model of Friedreich Ataxia. Hum Gene Ther. 2026 Aug 9:10430342261474315. doi: 10.1177/10430342261474315. Epub ahead of print. PMID: 42572232. 

Although gene therapy strategies aimed at restoring FXN have shown promise, excessive expression can lead to mitochondrial dysfunction, emphasizing the importance of maintaining FXN within a physiological range. Here, we evaluated a gene therapy approach based on a human mini-frataxin construct (miniFXN7) incorporating an endogenous regulatory element to enable controlled FXN expression. The construct was delivered systemically using an AAV-PHP.eB vector in the Pvalb-cKO mouse model of FA. MiniFXN7 treatment resulted in widespread neuronal transduction and restoration of FXN expression toward a near-physiological range in the neuronal populations examined. Treated mice exhibited sustained improvements in motor coordination and proprioceptive function, including normalization of H-reflex responses. At the cellular level, miniFXN7 restored succinate dehydrogenase activity, a mitochondrial Fe-S enzyme, and was associated with partial normalization of mitochondrial morphology. In parallel, neuronal integrity was preserved and astrogliosis reduced across the cerebellum. These findings demonstrate that physiologically regulated FXN replacement is sufficient to achieve substantial functional rescue in FA, supporting a gene therapy strategy based on a transgene expression driven by endogenous regulatory elements.

Directional information flow in human frataxin defines allosteric pathways connecting the hydrophobic core to the iron-binding ridge

Kırboğa KK, Küçüksille EU. Directional information flow in human frataxin defines allosteric pathways connecting the hydrophobic core to the iron-binding ridge. FEBS J. 2026 Aug 13. doi: 10.1111/febs.70687. Epub ahead of print. PMID: 42593048. 

We identify LEU47 (LEU136 in UniProt Q16595 numbering) and LEU51 (LEU140) as primary signal sources with net transfer entropy values of 0.415 and 0.249, respectively, connecting the hydrophobic core to the iron-binding acidic ridge. NMR relaxation at 600 and 800 MHz reveals elevated R2/R1 ratios (9.90-10.00) and significant exchange contributions (Rex = 3-5 s-1) specifically at these primary signal source residues, indicating μs-ms dynamics. Hydrogen-deuterium exchange mass spectrometry demonstrates that hub residues possess intermediate protection factors (ln(PF) = 5.97-6.07) optimal for conformational signaling, while iron binding induces bidirectional protection changes propagating through the identified pathway. Systematic mutagenesis confirms that disruption of hub residues reduces iron-binding affinity 1.9-4.2-fold and decreases thermal stability by 4.3-11.2 °C, despite occupying buried-core positions distant from the iron-coordinating acidic-ridge residues (LEU136/LEU140 Cα to ASP122, ASP124, and GLU189 = 6.7 to 11.8 Å in PDB 1EKG). The strong prediction-experiment correlation establishes transfer entropy as a reliable predictor of functionally important allosteric residues and provides a methodological framework applicable to other proteins of biomedical significance.

Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease

Cho, H., Sayana, R., Koladiya, A. et al. Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease. Nat Commun (2026). doi:10.1038/s41467-026-76775-y 

 Here we show that myeloid cell replacement promotes neurological and cardiac recovery in FA mice through intercellular mitochondrial transfer. Donor-derived mitochondria are transferred from microglia and macrophages to central nervous system cells and cardiomyocytes, increasing oxidative phosphorylation and ATP synthesis gene expression and mitochondrial protein abundance. These molecular changes are accompanied by improved survival and growth in male and female mice and enhanced spontaneous locomotion, strength, coordination and cardiac and function in female mice. In cultured cells, mitochondrial transfer requires direct cell-cell contact and partially restores respiratory capacity in frataxin-deficient recipient cells, which exhibit enhanced mitochondrial uptake, suggesting disease-specific mechanisms that promote mitochondrial acquisition or retention. These findings identify mitochondrial transfer as a mechanism underlying the therapeutic effects of myeloid cell replacement and support hematopoietic transplantation for FA and other mitochondrial disorders.

Allosteric rewiring of mitochondrial stress signaling through Miro1

Drwesh L, Fitzgerald J; Allosteric rewiring of mitochondrial stress signaling through Miro1: Cell Chemical Biology, 33, 1071-1073. doi:10.1016/j.chembiol.2026.07.011 

 Mitochondrial dysfunction is a common feature of both inherited mitochondrial disorders and neurodegenerative diseases. Although these disorders differ clinically, many converge on shared underlying pathobiology, including oxidative damage, impaired mitochondrial homeostasis, and defective mitochondrial quality control. Chandra and colleagues investigate these shared stress pathways in the context of Friedreich’s ataxia.

Unlocking Sulforaphane’s Potential in Friedreich Ataxia: Further Evidence from Preclinical Investigations Using Induced Pluripotent Stem Cell-Derived Sensory Neurons

Yang W, Thompson B, Miellet S, et al. Unlocking Sulforaphane’s Potential in Friedreich Ataxia: Further Evidence from Preclinical Investigations Using Induced Pluripotent Stem Cell-Derived Sensory Neurons. Antioxidants & Redox Signaling. 2026;0(0). doi:10.1177/15230864261470377 

 In FA1, SF treatment improved cell viability and reduced oxidative stress and inflammation. In FA3, SF increased cell viability, FXN protein levels, and gene and protein expression of redox markers, while targeting dysregulated epigenetic mechanisms and inflammation. All three lines showed SF’s consistent anti-oxidant and anti-inflammatory effects. Responses to Omav and DMF varied across the FA lines with less pronounced effects than when treated with SF. Overall, SF was more effective than Omav and DMF in improving cell viability and regulating FXN expression and epigenetic, redox, and inflammatory pathways.

Graviton BioScience Announces Clearance of Investigational New Drug (IND) for GV101 for the Treatment of Friedreich's Ataxia

NEW YORK, Aug. 11, 2026 /PRNewswire/ -- Graviton BioScience Corporation, a privately held, clinical-stage biotechnology company developing a diverse pipeline of therapeutics, including selective ROCK2 inhibitors for metabolic, inflammatory, fibrotic, and central nervous system disorders, announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a novel capsule formulation of GV101, a proprietary oral ROCK2 inhibitor being developed for Friedreich's ataxia (FA). This new formulation of GV101 was specifically optimized for development in FA and other potential orphan indications. Preclinical and clinical studies have demonstrated that GV101 increases frataxin protein levels, which is a potentially disease modifying therapeutic approach that addresses the root cause of Friedreich's ataxia (FA). Following the FDA's 30-day review period, Graviton received IND clearance on August 7, 2026, enabling the initiation of a Phase 2 clinical study in individuals living with FA. 

 Graviton now plans to initiate a 12-week, randomized, placebo-controlled, dose-finding Phase 2 trial enrolling up to 48 participants at multiple sites in the United States and internationally. The study is designed to evaluate the efficacy, safety, and tolerability of a range of GV101 capsule doses in individuals living with Friedreich's ataxia. The primary endpoint is an increase from baseline in frataxin levels measured in patients' cells.

Assessing airway clearance dysfunction in Friedreich's ataxia: A focus on peak cough flow

Smith BK, Coker MA, Liberati C, Meyer BP, Norman S, Ehrbar J, Leon-Astudillo C, Subramony S, Corti M. Assessing airway clearance dysfunction in Friedreich's ataxia: A focus on peak cough flow. J Neuromuscul Dis. 2026 Jun 8:22143602261452334. doi: 10.1177/22143602261452334. Epub ahead of print. PMID: 42253100; PMCID: PMC13437907. 

The study demonstrates respiratory dysfunction in patients with FRDA, and shows that disease severity and muscle weakness affect airway clearance. PCF is a more direct and clinically meaningful indicator of cough effectiveness than FVCpp. Comprehensive respiratory evaluations, including muscle-strength testing, can identify individuals who may benefit from targeted interventions to prevent complications.

Impaired Glur2 palmitoylation in cerebellar Purkinje cells of a Friedreich ataxia mouse model

Elizabeth Mercado-Ayón, Jennifer Coulman, Jia-Ying Lee, Eunjoo Lancaster, Elliot Goga, Mohammad Asad, Eric Witze, David R. Lynch, Impaired Glur2 palmitoylation in cerebellar Purkinje cells of a Friedreich ataxia mouse model, Experimental Neurology, 2026, 115955, ISSN 0014-4886, doi:10.1016/j.expneurol.2026.115955.

Mechanistically, reduced GluR2 palmitoylation associates with decreased expression and palmitoylation of the palmitoyl acyltransferase DHHC3, while levels of depalmitoylating enzymes remain unchanged. In vitro, DHHC3 enhances GluR2 palmitoylation, supporting a direct enzymatic relationship. Partial restoration of frataxin expression rescues GluR2 and DHHC3 protein levels and partially restores GluR2 palmitoylation. These findings identify impaired GluR2 palmitoylation as an early, selective synaptic alteration in FRDA and implicate dysregulated lipid-dependent post-translational modification as a mechanism linking frataxin deficiency to cerebellar synaptic vulnerability.

Partial bypass of frataxin deficiency by ISCU M141I restores cytosolic and nuclear Fe–S cluster assembly

Mosbach, V., Maio, N., Hermet, L. et al. Partial bypass of frataxin deficiency by ISCU M141I restores cytosolic and nuclear Fe–S cluster assembly. Cell Death Differ (2026). doi:10.1038/s41418-026-01832-4  

Results reveal a previously unrecognized compartment-specific rescue of Fe-S cluster dependent processes by the ISCU M141I variant in mammalian cells, raising for the first time the possibility of compartmental regulation of Fe-S cluster biogenesis.

Autophagy activation by urolithin-a derivative UA-36 mitigates Friedreich's ataxia pathologies induced by frataxin deficiency

Gong Q, Liu T, Han X, Zhang R, Liu X, Xiong B, Ali T, Huang J, Xie Y, Li S, Yang X. Autophagy activation by urolithin-a derivative UA-36 mitigates Friedreich's ataxia pathologies induced by frataxin deficiency. Mol Biomed. 2026 Jun 4;7(1):82. doi: 10.1186/s43556-026-00457-w. PMID: 42240896; PMCID: PMC13237351. 

 Here, we investigate the therapeutic efficacy and underlying mechanisms of UA-36, a novel water-soluble and bioavailable derivative of urolithin A, in cellular and animal models of FA. In Fxn-knockdown N2a cells, UA-36 significantly restored FXN protein levels, enhanced autophagic flux, improved mitochondrial function, and attenuated oxidative stress–induced damage. In vivo, oral administration of UA-36 for eight weeks in YG8R transgenic mice, a well-established FA model, markedly improved motor coordination, gait performance, and skeletal muscle strength. Histological and ultrastructural analyses revealed substantial protection against cerebellar Purkinje cell loss and iron deposition, cardiac hypertrophy, and the degree of skeletal muscle atrophy and fibrosis. Proteomic analysis of cerebellar tissue demonstrated that UA-36 robustly reprograms the FA-associated molecular landscape by upregulating pathways related to autophagy, mitochondrial biogenesis, oxidative phosphorylation, and redox homeostasis, while suppressing apoptosis and neuroinflammatory signaling. Together, these findings identify UA-36 as a promising lead compound and provide compelling evidence that therapeutic enhancement of autophagy and mitochondrial quality control represents a viable, mechanism-based strategy for the treatment of FA.

Visual Pathways Involvement in Friedreich’s Ataxia Patients Without Macular Impairment

Parisi, V.; Barbano, L.; Di Renzo, A.; Dell’Aquila, C.; D’Andrea, M.; Castelluzzo, A.M.; Colacino, G.; Gioiosa, V.; Coppola, G.; Casali, C.; et al. Visual Pathways Involvement in Friedreich’s Ataxia Patients Without Macular Impairment. J. Clin. Med. 2026, 15, 6097. doi:10.3390/jcm15156097 

 Fourteen FA patients (14 eyes; mean age 38.64 ± 8.21 years) without functional or structural macular abnormalities, confirmed by multifocal electroretinogram (mfERG) and spectral domain–optical coherence tomography (SD-OCT), and 20 age-matched healthy controls were enrolled. Patients were classified as late-onset (FA1, disease onset > 25 years) or early-onset (FA2, disease onset < 25 years). All participants underwent comprehensive ophthalmological and neurological evaluations. RGC function and visual pathway conduction were assessed through simultaneous pattern electroretinogram (PERG) and VEP recordings using 60′ and 15′ checkerboard stimuli. Retino-cortical time (RCT) was calculated as the difference between VEP P100 and PERG P50 implicit times. Statistical analyses included a general linear model. Results: 60′ PERG amplitude (A) was significantly (p < 0.01) reduced in the FA group compared to the Control group. FA patients showed significantly delayed 60′ and 15′ VEP ITs and significantly increased 60′ and 15′ RCT values, particularly in the FA1 group. In late-onset patients, no significant relationships were found between age at onset of disease and all electrophysiological parameters (60′ and 15′ VEP and PERG ITs and As and RCTs). Conclusions: In our selected FA, RCG function and neural conduction along the post-retinal visual pathways are impaired. The abnormal neuronal conduction is greater in late-onset FA patients and is not related to patients’ age and the age at the onset of the disease. The duration of the disease has a slight effect on the post-retinal neural conduction on small optic nerve fibers.

BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin

Brandon, C.J., Robinson-Thiewes, S., Kaulage, M. et al. BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin. Nat Cell Biol (2026). doi:10.1038/s41556-026-02044-1 

 How genes are desilenced without erasure of repressive chromatin is a poorly understood phenomenon. A dominant mode of repression occurs through methylation of lysine 9 of histone H3 (H3K9me3), a mark that engages heterochromatin protein 1 (HP1) to drive chromatin compaction and transcriptional silencing. The erasure and replacement of this repressive mark with acetyl/acyl groups recruits positive factors such as BRD4/BET to elicit gene transcription. Here we report that, in Friedreich’s ataxia, a synthetic gene regulator (SynGR1/SynTEF1) licenses transcription across repressive chromatin without removal or replacement of H3K9me3 or HP1. By recruiting BRD4/BET into repressive GAA repeats in frataxin (FXN), SynGR1 creates a paradoxical state wherein gene transcription and repressive chromatin coexist. Contrary to convention, we find that BRD4 partitions into phase separated HP1 condensates in vitro and into HP1 puncta in patient-derived cells, thus offering a mechanistic explanation for desilencing transcription without the dispersal of mesoscale repressive chromatin. More broadly, our study highlights the dynamic nature of repressive chromatin and the context dependence of epigenetic marks in regulating gene expression

Larimar Therapeutics Reports Second Quarter 2026 Financial and Business Update

BALA CYNWYD, Pa., Aug. 04, 2026 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar). “Open label (OL) study data announced in June further reinforce the disease-modifying potential of nomlabofusp, demonstrating continued directional improvements in key clinical endpoints over time alongside a well-characterized safety profile. Following receipt of minutes from a successful Type B multidisciplinary pre-BLA meeting with the Food and Drug Administration (FDA), the first module of our rolling Biologics License Application (BLA) has been submitted, with completion expected in the second half of 2026. We continue to see strong enthusiasm from patients and investigators as we advance the OL study with additional participants dosed in July and several adults and adolescents in screening. We are also on track to initiate dosing in our global confirmatory study this quarter. Looking ahead, we are focused on execution as we work to bring forward nomlabofusp as the first potential therapy to address the underlying cause of disease for pediatric and adult patients living with Friedreich’s ataxia (FA).”

Stem Cell Transplantation in Friedreich Ataxia: Cure for Leukemia but No Effect on Neurological Progression

A. Gitman, N. Bhandari, M. Castellaro, K. Schadt, M. Cancio, and D. R. Lynch, “ Stem Cell Transplantation in Friedreich Ataxia: Cure for Leukemia but No Effect on Neurological Progression,” Annals of Clinical and Translational Neurology (2026): 1–3, doi:10.1002/acn3.70455. 

After the transplant, her neurologic disease progressed similarly to other patients, but her blood frataxin levels returned to normal and cardiac hypertrophy decreased. This shows that FRDA patients can be treated with bone marrow transplantation, but such treatment alone has no direct effect on progression of neurologic disease.

Adjuvia Therapeutics Closes $8 Million Series Seed Financing to Advance Novel Mitochondrial Disease Therapy into the Clinic

Jul 29, 2026. SAN FRANCISCO--(BUSINESS WIRE)--Adjuvia Therapeutics, a biotechnology company developing therapeutics to treat mitochondrial dysfunction and disease, today announced the closing of an $8 million Series Seed financing. The financing will support the submission of an Investigational New Drug (IND) application for Adjuvia's lead candidate, ATI-105, later this summer, followed by the initiation of the Phase 1 clinical trial in healthy volunteers in Fall 2026. Adjuvia also plans to begin a Phase 1/2 study in patients with Friedreich's ataxia in early 2027.

Goldenrod Therapeuticsare committed to developing a next-generation phosphodiesterase 4 (PDE4) inhibitor designed to address serious neurological conditions, including Friedreich’s ataxia

Goldenrod Therapeutics is a portfolio company of Fannin based in Houston, Texas. We are committed to developing a next-generation phosphodiesterase 4 (PDE4) inhibitor designed to address serious neurological conditions, including Friedreich’s ataxia, other neurodegenerative diseases, substance use disorders (SUDs), and pain. 

Neurophysiological assessment of disease severity in Friedreich’s Ataxia: a study of brainstem auditory and visual evoked potentials

Maccora S, Quartetti U, Lima SM, Rini N, Cucchiara M, Agnello L, Gambino CM, Brighina F, Ciaccio M, Di Stefano V. Neurophysiological assessment of disease severity in Friedreich's Ataxia: a study of brainstem auditory and visual evoked potentials. Clin Neurophysiol. 2026 Aug;188:2111933. doi: 10.1016/j.clinph.2026.2111933. Epub 2026 May 14. PMID: 42143837. 

 BAEPs and p-VEPs are highly prevalent and closely associated with clinical severity in chronic FRDA, outperforming tested serum biomarkers. Evoked potentials provide accessible, non-invasive, quantitative candidate biomarkers for severity assessment and longitudinal monitoring in FRDA, supporting their use in clinical practice and trial design when fluid markers are inconclusive.

Omaveloxolone Driven NRF2 Activation as a Novel Therapeutic Strategy for Pulmonary Hypertension

Omaveloxolone Driven NRF2 Activation as a Novel Therapeutic Strategy for Pulmonary Hypertension. Huang, Chuangjia, Bai, June, Luo, Ang, Yang, Lei, Wang, Xingting, Dang, Linlin, Bao, Changlei, Zhu, Jinsheng, Chen, Zixuan, Wu, Bitao, Long, Jintao, Feng, Jieyi, Luo, Zinan, Xiao, Yingying, Sun, Hanliang, Liang, Shuxin, Zhang, Li, Hua, Jing, Gou, Demin, Desai, Ankit A., Li, Li, Zhang, Caojin, Chu, Aiai, Tang, Haiyangdoi:10.1161/HYPERTENSIONAHA.126.26711 Published Online: 2026-07-27 

 NRF2 expression and nuclear localization were reduced in PH lungs and hypoxia-exposed cells, whereas Omaveloxolone restored NRF2 activity and increased downstream antioxidant enzymes. In endothelial cells, Omaveloxolone reduced oxidative stress, suppressed inflammatory signaling, and inhibited endothelial-to-mesenchymal transition. In smooth muscle cells, it attenuated oxidative stress and normalized abnormal proliferation, migration, and apoptosis. Omaveloxolone reduced HIF (hypoxia-inducible factor)-2α accumulation in endothelial cells and inhibited HIF-1α stabilization in smooth muscle cells. NRF2 knockdown attenuated these effects, supporting pathway dependency. Omaveloxolone attenuated PH, reduced right ventricular hypertrophy and vascular remodeling, and improved right ventricular function across hypoxia, monocrotaline, and sugen/hypoxia models under both preventive and therapeutic regimens.

Larimar Therapeutics Reports Positive Open Label Data and Submission of First Module of Rolling BLA for Accelerated Approval of Nomlabofusp for Friedreich’s Ataxia

June 29, 2026. BALA CYNWYD, Pa., June 29, 2026 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar)  a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced it has submitted the first module of its rolling Biologics License Application (BLA) submission to the Food and Drug Administration (FDA) for accelerated approval of nomlabofusp. The OL study is evaluating the safety and tolerability, pharmacokinetics (PK), and frataxin (FXN) levels in skin and buccal cells, along with exploratory pharmacodynamic (PD) markers (lipid profiles and gene expression) and clinical outcomes following long-term subcutaneous administration of nomlabofusp. The OL study protocol has now been amended to include children 2-11 years of age, adolescents and adults who have not participated in a prior nomlabofusp study.

Characterizing Friedreich’s ataxia cardiomyopathy with serial cardiac magnetic resonance imagings

Cripe, L. H., Alvarado, C., Hayes, E. A., Krishnamurthy, R., Gunsaulus, M. E., Waldrop, M. A., & Nandi, D. (2026). Characterizing Friedreich’s ataxia cardiomyopathy with serial cardiac magnetic resonance imagings. Annals of Pediatric Cardiology, 19(4), 364–373. doi:10.4103/apc.apc_22_26 

In this exploratory study, CMR demonstrated patterns of septal hypertrophy, lateral wall fibrosis, and trends toward declining ventricular function. Findings were largely nonsignificant and should be considered hypothesis-generating. Larger, multicenter studies are needed to clarify the role of CMR in disease progression and clinical management.

Effects of Friedeich Ataxia on the Interrelations Between Left Ventricular Length and Long-Axis Systolic and Diastolic Excursions

R. Peverill, Effects of Friedeich Ataxia on the Interrelations Between Left Ventricular Length and Long-Axis Systolic and Diastolic Excursions, Heart, Lung and Circulation, Volume 35, Supplement 3, 2026, Page S142, doi:10.1016/j.hlc.2026.07.126. 

 Features of long-axis dysfunction in FRDA include: (i) a smaller contraction amplitude, which is partly attributable to a smaller LVEDL, and therefore has both structural and functional elements, (ii) smaller early diastolic excursion which is fully accounted for by smaller long-axis contraction, and (iii) lack of any compensatory increase in LA contraction, which is consistent with the presence of a concomitant LA myopathy.

Cardiomyocyte Dysfunction is Modulated by PCDHGA10 in Friedreich Ataxia,

J. Lees, H. Zhang, L. Jiao, A. Kong, R. Phang, L. Li, N. Su, A. Mukhtar, S. Bass-Stringer, A. Pébay, M. Dottori, L. Corben, M. Delatycki, R. Peverill, S. Wilcox, J. Choi, J. Pullin, D. McCarthy, J. Napierala, M. Napierala, S. Lim, Cardiomyocyte Dysfunction is Modulated by PCDHGA10 in Friedreich Ataxia, Heart, Lung and Circulation, Volume 35, Supplement 3, 2026, Pages S709-S710, doi:10.1016/j.hlc.2026.07.1148. 

Our human iPSC model captures early, clinically relevant features of FRDA cardiomyopathy and identifies PCDHGA10 as a disease-associated target within the γ-protocadherin family of calcium-dependent adhesion molecules. siRNA-mediated PCDHGA10 knockdown rescued cell survival, diastolic dysfunction, and mitochondrial ROS levels, implicating Ca2+-coupled and redox-linked phenotypes in cardiomyocyte dysfunction. These findings support further mechanistic study and therapeutic exploration of PCDHGA10

Design Therapeutics Provides RESTORE-FA Clinical Development Update and Reports Second Quarter 2026 Financial Results

CARLSBAD, Calif., Aug. 03, 2026 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc..Positive 

RESTORE-FA Four-Week Data Support Advancement of DT-216P2. As reported in May 2026, DT-216P2 was generally well-tolerated and demonstrated dose-dependent increases in endogenous frataxin mRNA and protein levels, together with improvements across multiple clinical measures following four weeks of intravenous dosing in patients with Friedreich ataxia. 

Modifications to RESTORE-FA. Based on the four-week data, Design is modifying the ongoing cohorts in the RESTORE-FA trial to support the next stage of clinical development. The study will continue to evaluate 1 mpk as the planned go-forward dose, with the intention of enrolling 10 patients in the 12-week cohort. In addition, modifications include specifying endogenous blood FXN protein percent change from baseline as the primary efficacy endpoint and exploring a dose level above 1 mpk. 

Next Steps and Expected Milestones: Design expects to provide an update on its registrational plans in the fourth quarter of 2026, with data following 12 weeks of treatment expected in the first quarter of 2027.

Towards routine genetic testing of repeat expansions in neurogenetic diseases using multiplex CRISPR-Cas9-targeted long read sequencing

Fergelot, P., Boury, C., Penaud, B. et al. Towards routine genetic testing of repeat expansions in neurogenetic diseases using multiplex CRISPR-Cas9-targeted long read sequencing. Sci Rep (2026). doi:10.1038/s41598-026-64095-6 

 We simultaneously targeted nine loci involved in 10 repeat expansion disorders in a single capture panel, including FMR1, HTT, DMPK, CNBP/ZNF9, ATXN2, JPH3, FXN, C9ORF72 and RFC1, covering a broad range of repeat types, sizes and diagnostic needs. Results were compared with standard routine testing methods.

Clinical Challenges in Managing Diabetes Mellitus in Friedreich’s Ataxia

Aarya Naik, MBBS, Hooman Oktaei, MD, Clinical Challenges in Managing Diabetes Mellitus in Friedreich’s Ataxia, Endocrine Practice , 32, S66-S67. doi:10.1016/j.eprac.2026.01.168 

Friedreich’s ataxia (FRDA) is a multisystem disease, with ataxia being the most overt clinical feature. It can be complicated by diabetes mellitus. FRDA-related diabetes has been reported in 5% to 40% of children and adults. Despite the clinical relevance of FRDA-related diabetes mellitus, no evidence-based clinical practice guidelines for screening or management have been set.