69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia

2026 Annual Meeting of the American Society of Gene and Cell Therapy: ASGCT 2026 Annual Meeting Abstracts. Available online 8 May 2026, Version of Record 8 May 2026. 

 69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia. 69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia. Jon Dempersmier, Mariam Elhawary, Ian McLachlan, Hayley Ulloa, Kai Li, Diane Hamann, Zhiping Weng, Ricardo Mouro Pinto, Travis Wager, Simon Xi, Sam Hasson; 

Friedreich’s ataxia (FA) represents a compelling use case for regulated gene therapy. FA is an autosomal recessive disorder caused by repeat expansion–mediated silencing of the FXN gene, resulting in impaired iron–sulfur cluster biogenesis, mitochondrial dysfunction, neurodegeneration, and cardiomyopathy. While constitutive AAV-mediated FXN replacement has shown efficacy in preclinical models, excessive Frataxin expression has been associated with cardiotoxicity, highlighting the need for controlled dosing.

This system consists of DNA-encoded regulatory elements, termed RSwitches, which are selectively modulated by matched synthetic small molecules, or RDrugs, in a dose-dependent manner. RDrugs direct specific pre-mRNA splicing events required for productive transgene expression, enabling temporal control on the order of hours and quantitative control of protein output almost five orders of magnitude from AAV vectors.

62 Development and Translation of PPL-001, an autologous, gene-edited CD34+ hematopoietic stem cell Therapy for Friedreich’s Ataxia

2026 Annual Meeting of the American Society of Gene and Cell Therapy: ASGCT 2026 Annual Meeting Abstracts. Available online 8 May 2026, Version of Record 8 May 2026.  62 

Development and Translation of PPL-001, an autologous, gene-edited CD34+ hematopoietic stem cell Therapy for Friedreich’s Ataxia  Anusha Sivakumar, Colin Exline, Stephanie Cherqui.

 Here, we present a GMP-compliant, commercially/clinically scalable manufacturing process and safety data of PPL-001, aimed at initiating the first-in-human HSPC and genome editing clinical trial for FRDA. 

These promising results of scale-up feasibility and safety support our efforts in clinical translation of CRISPR/Cas9 gene edited CD34+ HSPCs as a novel treatment approach for Friedreich’s ataxia.

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

Simona Maccora, Umberto Quartetti, Salvatore Maria Lima, Nicasio Rini, Marco Cucchiara, Luisa Agnello, Caterina Maria Gambino, Filippo Brighina, Marcello Ciaccio, Vincenzo Di Stefano, Neurophysiological assessment of disease severity in Friedreich’s Ataxia: a study of brainstem auditory and visual evoked potentials, Clinical Neurophysiology, 2026, 2111933, ISSN 1388-2457, doi:10.1016/j.clinph.2026.2111933.

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.

Experimental gene therapy raises hope for children with fatal neurological disease

Brunel University of London. By Press Officen14 May 2026. 

Scientists at Brunel University of London and University College London Great Ormond Street Institute of Child Health have developed an experimental stem cell treatment for Friedreich’s ataxia.

The findings suggest the technique could eventually be delivered using a patient’s own cells, reducing the risk of the body rejecting the therapy after transplantation.The researchers removed blood-forming stem cells and modified them in the laboratory using a virus to deliver an engineered frataxin protein.  This new engineered version of frataxin can be secreted by blood cells and absorbed by other tissues, allowing it to reach vital organs such as the brain, heart and muscles.

Validation of circulating miR-323a-3p and miR-625-3p to classify hypertrophic cardiomyopathy in Friedreich’s ataxia

Ibáñez-Cabellos, J.S., Baviera-Muñoz, R., Alemany-Perna, B. et al. Validation of circulating miR-323a-3p and miR-625-3p to classify hypertrophic cardiomyopathy in Friedreich’s ataxia. Sci Rep 16, 15056 (2026). doi:10.1038/s41598-026-50975-4 

 This study validates a genetic blood "signature" that assists clinicians in identifying patients with Friedreich's Ataxia (FRDA) who are developing cardiac or metabolic complications. 

The research explores the use of microRNAs as non-invasive biomarkers, aiming to identify blood indicators more accurate than current standards, such as troponin, for diagnosing hypertrophic cardiomyopathy and diabetes. 

 Notably, the combination of two specific microRNAs (miR-323a-3p and miR-625-3p) demonstrated a superior ability to classify and predict HCM, outperforming traditional protein biomarkers. 

Furthermore, the study confirmed that other microRNAs, such as miR-128-3p and miR-130b-5p, are significantly elevated in patients suffering from both ataxia and diabetes.

Pharmacological treatments for Friedreich ataxia ( Cochrane Database of Systematic Reviews 2026)

Lyons S, Kearney M, Fahey MC, Janjal P, Pandolfo M, Patton P. Pharmacological treatments for Friedreich ataxia. Cochrane Database of Systematic Reviews 2026, Issue 5. Art. No.: CD007791. DOI: 10.1002/14651858.CD007791.pub5. Accessed 12 May 2026.

In this updated Cochrane systematic review, meta‐analysis of results on the ataxia rating scale showed that pharmacological treatments probably make little or no difference compared with placebo after 12 months of treatment. Given this result, the probable improvement that we found in upper limb dexterity was unexpected. Treatment‐emergent adverse events leading to cessation of medication or death may be no more common in treatment groups than placebo groups as there were few adverse events detected in the treated groups. However, the studies may not have detected all rare and serious adverse events.

Transcription and Cohesin Direct Domain Boundary Spatial Positioning and are Linked to Friedreich's Ataxia

Ashley Karnay, Ricardo Linares-Saldana, Qiaohong Wang, Zachary Gardner, Jialiu A. Liang, Garrett T. Santini, Krishna Kumar Haridhasapavalan, Son C. Nguyen, Siewert Hugelier, Bhavana Shewale, Masato T. Kanemaki, Jill S. Napierala, Marek Napierala, Robert B. Wilson, Nicole Dubois, Andrey Poleshko, Wonho Kim, Parisha P. Shah, Melike Lakadamyali, Eric F. Joyce, Rajan Jain, Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich’s ataxia, Molecular Cell, 2026, DOI: 10.1016/j.molcel.2026.04.019. 

These results suggest that gene silencing in Friedreich's ataxia is reinforced by where the gene sits in the nucleus," said Ashley Karnay, Ph.D., a postdoctoral fellow in Cardiovascular Medicine and Cell & Developmental Biology and the study's lead author. "By changing that positioning, we can partially restore FXN gene activity in diseased cells." 

 While the findings are early and not a treatment, they point to genome organization itself as a contributor to disease and raise the exciting possibility that future therapies could work by changing how the DNA is organized inside the nucleus.

442 FRATAXIN IS DOWNREGULATED IN COLONIC INFLAMMATION DISRUPTING EPITHELIAL HOMEOSTASIS

Mo Wang, Xinqian Meng, Qiong Guo, Chunyan Peng, LEI WANG; 442 FRATAXIN IS DOWNREGULATED IN COLONIC INFLAMMATION DISRUPTING EPITHELIAL HOMEOSTASIS, Gastrointestinal Endoscopy, Volume 103, Issue 5, Supplement, 2026, Page S-882, ISSN 0016-5107, doi: 10.1016/S0016-5107(26)02275-3. 

This study identifies a novel link between frataxin (FXN) and ulcerative colitis (UC), demonstrating that its role extends beyond the nervous system and heart to intestinal health.

In Colonic Inflammation, FXN levels are drastically reduced in the colonic mucosa of patients with active UC, lower frataxin levels correlate directly with increased inflammatory severity.

Pathogenesis, FXN deficiency triggers mitochondrial energy failure and oxidative stress within the gut, compromising the epithelial barrier and inducing cell death. 

Conclusion: Frataxin is essential for colonic homeostasis. This suggests the FXN pathway as a potential therapeutic target for inflammatory bowel diseases and provides a mechanistic explanation for gastrointestinal complications in Friedreich’s Ataxia patients.

CGG, CAG, and GAA: Genome-wide comparison of the disease linked trinucleotide short tandem repeats

Annear DJ, Vandeweyer G, Kooy RF. CGG, CAG, and GAA: Genome-wide comparison of the disease linked trinucleotide short tandem repeats. BMC Genomics. 2026 Feb 18;27(1):302. doi: 10.1186/s12864-026-12651-9. PMID: 41709137; PMCID: PMC13020279. 

This paper offers a new genomic perspective on Friedreich's Ataxia by analyzing the behavior of the GAA triplet in comparison to other pathogenic repeats (such as Huntington's CAG).

This study highlights that Friedreich's Ataxia (FRDA) is unique due to the specific nature of the GAA repeat, setting it apart from other repeat-expansion diseases:

- Extreme Instability: GAA is the most abundant and polymorphic triplet in the human genome, explaining its intrinsic tendency for the pathological expansion found in the FXN gene. 

- Key Location: Unlike other repeats, GAA sequences are concentrated in introns, validating why FRDA results in gene silencing rather than direct protein alteration. 

FRDA is not merely a genetic error but a consequence of the evolutionary fragility of the GAA sequence, necessitating DNA-stabilization-specific therapeutic

Comprehensive Review of Anesthetic Strategies for Patients With Neurodegenerative Diseases

Grabarczyk Ł. Comprehensive Review of Anesthetic Strategies for Patients With Neurodegenerative Diseases. Med Sci Monit. 2026 Apr 11;32:e950453. doi: 10.12659/MSM.950453. PMID: 41964193; PMCID: PMC13081753.

This article aims to review the perioperative anesthetic management of patients with NDDs, including Huntington disease, (spino)cerebellar ataxia, Friedreich ataxia, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis.