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, Maddock M, Napierala M, Dottori M, Kwa FAA. Unlocking Sulforaphane's Potential in Friedreich Ataxia: Further Evidence from Preclinical Investigations Using Induced Pluripotent Stem Cell-Derived Sensory Neurons. Antioxid Redox Signal. 2026 Jul 20:15230864261470377. doi: 10.1177/15230864261470377. Epub ahead of print. PMID: 42473835.

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.

Cellares and Papillon Therapeutics Partner to Automate Manufacturing of PPL-001 for Patients With Friedreich’s Ataxia

SOUTH SAN FRANCISCO, Calif. & SAN DIEGO, Jul 21, 2026. Cellares, the first Integrated Development and Manufacturing Organization (IDMO), and Papillon Therapeutics Inc., a clinical-stage biotechnology company advancing a pipeline of multi-systemic genetic medicines directed at the underlying causes of inherited disease, today announced a collaboration to automate manufacturing of PPL-001, Papillon’s investigational gene-corrected hematopoietic stem and progenitor cell (HSPC) therapy targeting Friedreich’s ataxia.

Unveiling the idiographic portrait of Friedreich’s ataxia in an Omani patient: A multidisciplinary case study

Al Azri, F. H., Otaify, G. A., AlRiyami, M., Gujjar, A. R., ALBusaidi, A., Al Kindi, F. A., Rajeev, N., Al Busaidi, S. J., Bolourkesh, H., Ambusaidi, A., Al Jahwari, N. A., Al-Wardy, M., & Al-Adawi, S. (2026). Unveiling the idiographic portrait of Friedreich’s ataxia in an Omani patient: A multidisciplinary case study. International Journal of Nutrition, Pharmacology, Neurological Diseases, 16(1), 169–173. doi:10.4103/ijnpnd.ijnpnd_197_25 

This case report details the diagnostic journey of a 22-year-old Omani male with undiagnosed FA, highlighting the value of the idiographic approach within a biopsychosocial framework. Initially presenting with psychotic symptoms, the patient underwent a comprehensive interdisciplinary evaluation, revealing neurological and psychiatric manifestations. The case, set against the backdrop of the COVID-19 pandemic, emphasizes the influence of restricted healthcare access on disease progression. This report underscores the importance of recognizing atypical presentations of FA and highlights the role of a multidisciplinary team in navigating the complexities of this rare condition.

Precision therapeutics and innovative clinical trial design in neurodegenerative diseases

Ariadna Domínguez-García, Juan Carlos Delgado-Uriarte, Amin Cervantes-Arriaga, Precision therapeutics and innovative clinical trial design in neurodegenerative diseases, Revista de Investigación Clínica, Volume 78, Issue 4, 2026, 100050, ISSN 0034-8376, doi:10.1016/j.ric.2026.100050. 

This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.

Mitochondria setting the stage for ferroptosis

Ahola S. Mitochondria setting the stage for ferroptosis. Trends in Endocrinology & Metabolism, 2026; 0. Doi:10.1016/j.tem.2026.06.006 

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. Recent advances challenge the view of ferroptosis as a predominantly cytosolic process and instead position mitochondria as central regulators of ferroptosis by coordinating iron metabolism, lipid composition, and redox homoeostasis. This review discusses ferroptosis from a mitochondrial perspective and examines its potential relevance to primary mitochondrial diseases, where defects in oxidative phosphorylation profoundly remodel cellular metabolism and redox homoeostasis. The review highlights emerging roles for mitochondrial iron–sulfur cluster biogenesis, coenzyme Q metabolism and trafficking, mitochondrial lipid remodelling, and stress-response signalling in shaping ferroptotic vulnerability. Finally, we discuss current evidence linking ferroptosis to mitochondrial pathology and the therapeutic opportunities arising from targeting ferroptosis pathways in mitochondrial disease.

Domain Adaptation for IMU Data to Enhance Objective Assessment of Friedreich Ataxia

Tran, M., Ranaweera, K., Ngo, T., Pathirana, P., Milne, S., Horne, M., Delatycki, M., & Corben, L. (2026). Domain Adaptation for IMU Data to Enhance Objective Assessment of Friedreich Ataxia. IEEE Journal of Biomedical and Health Informatics, PP. doi:10.1109/JBHI.2026.3702417 

 Our approach leverages a convolutional neural network (CNN) architecture to automatically learn high-level representations from raw IMU signals, minimizing reliance on manual feature engineering. Central to our method is a two-stage training strategy that incorporates domain adversarial learning, enabling knowledge transfer between two IMU-based assessment tools: the Ataxia Instrumented Measures cup (AIM-C) and spoon (AIM-S). This strategy enhances learning from each device by exploiting shared underlying representations.

Epigenetic reactivation in Friedreich’s ataxia from benzamides to gene‑targeted chimeras

Ansari, F. U., Rojsajjakul, T., Liu, J., Nageshwaran, S. K., & Blair, I. A. (2026). Epigenetic reactivation in Friedreich’s ataxia from benzamides to gene‑targeted chimeras. Expert Opinion on Drug Discovery, 21(7), 779–791. doi:10.1080/17460441.2026.2689723 

 This review summarizes the evolution of FXN protein‑reactivating approaches from first‑generation systemic epigenetic therapies, including class I‑selective benzamide histone deacetylase inhibitors and high‑dose nicotinamide, to emerging locus‑targeted platforms such as anti‑gene oligonucleotides and gene‑targeted chimera small molecules. The authors also examine splice‑modulating strategies aimed at increasing the extra‑mitochondrial FXN‑E isoform, discuss delivery and safety challenges across modalities, and highlight biomarker frameworks integrating isoform‑resolved FXN protein measurements and chromatin readouts.

Advances in Gene and Cellular Therapy in Friedreich Ataxia

Lazaropoulos MP, Lynch DR. Advances in Gene and Cellular Therapy in Friedreich Ataxia. Mol Diagn Ther. 2026 Jun 29. doi: 10.1007/s40291-026-00854-5. Epub ahead of print. PMID: 42373844. 

 Multiple investigational techniques and strategies seek to permanently alter the disease course in patients with Friedreich ataxia, although no product has established definitive benefit. This review catalogs both the history and ongoing efforts of genetic and cellular therapies applied to Friedreich ataxia and its disease models, including therapeutic efficacy and adverse effects. We list the key limitations and cautions of such therapies, chiefly those of potential FXN overexpression toxicity, critical therapeutic windows, and adverse effects of these therapies applicable to any disease target. As gene and cellular therapy continue to diversify in design and strategy, Friedreich ataxia patients will likely have multiple therapeutic options in the future from both investigational therapies described here and future ones yet to be optimized.

Frataxin attenuates endothelial inflammation triggered by engulfment of senescent erythrocytes

Xingyi Cheng, Yi Cheng, Chenglin Huang, Tong Wei, Yuetong Guo, Jing Gao, Weili Shen, Frataxin attenuates endothelial inflammation triggered by engulfment of senescent erythrocytes, Free Radical Biology and Medicine, 2026,ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2026.07.006. 

Hypertension is linked to a shortened erythrocyte lifespan, with endothelial cells acting as non-professional phagocytes to clear senescent erythrocytes. However, whether increased erythrophagocytosis contributes to endothelial inflammation remains unclear. Frataxin (FXN) plays a crucial role in controlling iron balance and metabolism. This study investigated the role of FXN-mediated iron engulfment in regulating endothelial pro-inflammatory phenotype.

Key Interventions in Friedreich's Ataxia and Their Impact on Patient Outcomes: A Systematic Review

Sarwinska D, Buchholz M, Iskandar A, Grobe-Einsler M, Klockgether T, Faber J, Michalowsky B. Key Interventions in Friedreich's Ataxia and Their Impact on Patient Outcomes: A Systematic Review. Mov Disord. 2026 Jul 6. doi: 10.1002/mds.70423. Epub ahead of print. PMID: 42410955. 

Friedreich's ataxia (FA) is a rare neurodegenerative disease with multisystemic symptoms that requires multidisciplinary care. This systematic review summarizes available pharmacological and nonpharmacological interventions, their outcomes, and alignment with patient-centered care domains, as well as their impact on these domains.