Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside

Dong Y, Zheng M, Ding W, Guan H, Xiao J, Li F. Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside. Redox Biol. 2025 Feb 14;81:103551. doi: 10.1016/j.redox.2025.103551. Epub ahead of print. PMID: 39965404.

 Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanisms, and precautions of Nrf2 activators in treating rare iron overload diseases.

Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study

Zahir H, Murai M, Wu L, Valentine M, Hynes SM. Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study. Clin Transl Sci. 2025 Feb;18(2):e70139. doi: 10.1111/cts.70139. PMID: 39976332; PMCID: PMC11840845. 

No safety concerns were identified. Supratherapeutic omaveloxolone exposure that covers the worst-case clinical exposure did not cause a clinically significant QTc prolongation and was generally well tolerated.

Multiple Sclerosis in a Patient with Friedreich's Ataxia

Yu Y, Kushlaf H. Multiple Sclerosis in a Patient with Friedreich's Ataxia (P4-6.016). Neurology. 2024 Apr 9;102(7_supplement_1):3347. doi: 10.1212/WNL.0000000000205077. Epub 2024 Apr 9. PMID: 39977947. 

The definitive diagnosis of multiple sclerosis in a FRDA patient is novel and requires careful reconciliation of the symptoms, clinical exam findings, and ancillary testing. The development of symptoms incompatible with FRDA should prompt clinicians to consider additional neurologic diagnoses.

Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing

Rocha, D.L., Pinheiro, J.d., Furtado, G.V. et al. Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing. J Community Genet (2025). doi:10.1007/s12687-025-00777-4 

Healthcare delay (HCDe) is an important but not well-known issue in genetic disorders, especially in tandem nucleotide repeat expansion diseases (TNRED). We aimed to investigate it and determine whether predictive genetic testing (PGT) and other factors may impact HCDe.

Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues

Ercanbrack WS, Ramirez M, Dungan A, Gaul E, Ercanbrack SJ, Wingert RA. Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues. Tissue Barriers. 2025 Feb 21:2462357. doi: 10.1080/21688370.2025.2462357. Epub ahead of print. PMID: 39981684. 

Most FRDA patients suffer from loss of motor control, cardiomyopathy, scoliosis, foot deformities, and diabetes. In this review, we discuss the known features of FRDA pathology and the current understanding about the basis of these alterations.

FDA Accepts New Drug Application for Vatiquinone to Treat Friedreich Ataxia

February 19, 2025​. The FDA accepted a new drug application (NDA) for vatiquinone for the treatment of children and adults with Friedreich ataxia (FA) and granted it priority review. The drug has a Prescription Drug User Fee Act target action date of August 19, 2025. 

"The results of the extension studies provide further evidence of the potential benefit of vatiquinone in slowing disease progression," Klein said in a news release.4 "In addition, the strong safety profile of vatiquinone positions it to be a potentially meaningful therapy for all Friedreich ataxia patients, particularly children and adolescents for whom there are no approved therapies.”

Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis

Cory SA, Lin CW, Patra S, Havens SM, Putnam CD, Shirzadeh M, Russell DH, Barondeau DP. Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis. Biochemistry. 2025 Feb 5. doi: 10.1021/acs.biochem.4c00733. Epub ahead of print. PMID: 39909887.

We propose that eukaryotic cysteine desulfurases are unusual members of the morpheein class of enzymes that control their activity through their oligomeric state. Overall, the findings support architectural switching as a regulatory mechanism linked to FXN activation of the human Fe-S cluster biosynthetic complex and provide new opportunities for therapeutic interventions of the fatal neurodegenerative disease FRDA.

Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants

Zahir H, Murai M, Wu L, Valentine M, Hynes S. Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants. J Clin Pharmacol. 2025 Feb 7. doi: 10.1002/jcph.6189. Epub ahead of print. PMID: 39920097. 

 It is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro. Two drug-drug interaction studies (NCT04008186 and NCT05909644) were performed to evaluate (1) the effect of drug-metabolizing enzymes (DMEs) and drug transporter (DT) modulators on the pharmacokinetics of omaveloxolone and (2) the effect of omaveloxolone on the pharmacokinetics of DME and DT substrates. Additionally, the safety of coadministering these drugs with omaveloxolone was assessed.

Neurocrine Biosciences and Voyager Therapeutics to expect IND filings in 2025

February 13, 2025. 

“We are encouraged that our novel TRACER capsids continue to perform consistently across multiple programs, and we believe they have the potential to transform gene therapy for CNS diseases. We continue to expect IND filings in 2025 for our gene therapy candidates for GBA1 and FA, and in 2026 for VY1706,” said Sandrock, Jr., in the press release

Patient involvement in clinical trials: a paradigm shift in research

Pijuan, J., Palau, F. Patient involvement in clinical trials: a paradigm shift in research. Orphanet J Rare Dis 20, 63 (2025). doi:10.1186/s13023-025-03573-y 

 Establishing universal guidelines will help ensure that all stakeholders (patients, caregivers and health professionals) can engage meaningfully in the developmental processes of healthcare initiatives. Given that health and disease affect us all, fostering collective involvement is essential for driving progress in this field.

Living with Friedreich Ataxia: Carla, Maria and Nuria

Biogen. February 11, 2025

Watch below to hear Carla, Maria and Nuria share their stories of living with FA.

 

Editorial: The mechanistic investigation and emerging therapies for Friedreich’s ataxia

Dong Y, Chandran V, Soragni E and Lynch DR (2025) Editorial: The mechanistic investigation and emerging therapies for Friedreich’s ataxia. Front. Pharmacol. 16:1560808. doi: 10.3389/fphar.2025.1560808

KosBio is a pioneering biotechnology startup: to develop an innovative treatment for Friedreich’s Ataxia (FRDA)

KosBio is a pioneering biotechnology startup, born out of a deeply personal and transformative mission: to develop an innovative treatment for Friedreich’s Ataxia (FRDA), a rare and incurable neurodegenerative disease. Our founders, intimately connected to FRDA through their own family experiences, bring a unique level of commitment and dedication to this mission, distinguishing KosBio in the competitive biotech landscape. 

 Leading our therapeutic pipeline is KB-001(TM), a therapy based on repurposing an FDA-approved drug to activate a developmental signaling pathway relevant to FRDA. This strategic approach not only expedites the path to treatment but also reduces potential risks by leveraging existing approved drugs. 

In addition, KosBio is advancing the development of a series of novel, patented drugs (KB002-KB021). These drugs are projected to have significantly greater potency than KB-001(TM), marking a substantial advancement in our therapeutic arsenal.

Functional Characterization of Parallel Fiber-Purkinje Cell Synapses in Two Friedreich's Ataxia Mouse Models

Joseph DJ, Mercado-Ayon E, Flatley L, Viaene AN, Hordeaux J, Marsh ED, Lynch DR. Functional Characterization of Parallel Fiber-Purkinje Cell Synapses in Two Friedreich's Ataxia Mouse Models. Cerebellum. 2025 Feb 5;24(2):42. doi: 10.1007/s12311-025-01796-0. PMID: 39907933; PMCID: PMC11799031.

To investigate the neural circuit basis of this dysfunction, we employed field recordings to measure Purkinje cell (PC) function and synaptic properties along with western blotting and immunohistochemistry to determine their density and structure in two established FRDA mouse models, the shRNA-frataxin (FRDAkd) and the frataxin knock in-knockout (KIKO) mice. Western blotting demonstrated subtle changes in mitochondrial proteins and only a modest reduction in the density of calbindin positive cells PCs in the cerebellar cortex of the FRDAkd mice, with no change in the density of PCs in the KIKO mice. Though PC density differed slightly in the two models, field recordings of parallel fiber-PC synapses in the molecular layer demonstrated concordant hypo-excitability of basal synaptic transmission and impairments of long-term plasticity using induction protocols associated with both potentiation and depression of synaptic strength. These results indicate that synaptic instability might be a common feature in FRDA mouse models.

Heart Gene Therapy Astellas Withdrawing

Astellas Pharma Inc., February 4, 2025Q3 YTD/FY2024 Financial Results (pg 13 and 33)

Pandolfo M. Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery

Pandolfo M. Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery. Neurol Genet. 2025 Jan 13;11(1):e200236. doi: 10.1212/NXG.0000000000200236. PMID: 39810753; PMCID: PMC11731367. 

 Now, 28 years after the gene discovery, although much remains to be understood about the disease's mechanisms and the development of effective therapies, the progress is undeniable. A thriving community has emerged, uniting researchers, health care providers, industry professionals, individuals with FRDA, their families, and dedicated volunteers. With this collective effort, a cure is within reach.

Identification of strengths and weaknesses of the healthcare system for persons living with rare diseases in Catalonia (Spain), and recommendations to improve its comprehensive attention: the “acERca las enfermedades raras” project

Hernández-Rodríguez, J., Martínez-Valle, F., Acebes, X. et al. Identification of strengths and weaknesses of the healthcare system for persons living with rare diseases in Catalonia (Spain), and recommendations to improve its comprehensive attention: the “acERca las enfermedades raras” project. Orphanet J Rare Dis 20, 42 (2025). Doi:10.1186/s13023-024-03518-x 

 Based on the criteria of equity and equality for which a public healthcare must be guaranteed to all citizens, PLWRD have also the right to access to all the available resources in a way that is as agile and equal as for other patients. The expert participants considered that the current Catalan healthcare model for RDs consists of a pioneer and advanced plan, unique in Spain, consisting of a functional network of qualified reference centers (XUECs), following the European model of the ERN thematic areas.

Unraveling Mechanisms and Potential Treatment of Cardiomyopathy in Friedreich’s Ataxia

Published on January 30, 2025 in Cornerstone Blog. Studying both patient-derived cardiac cells and zebrafish models will help Drs. Wilson and Pei to identify potential inflammatory signaling that may exacerbate FA.

Jupiter Neurosciences partners with Zina for Parkinson's trial

Jupiter, Florida, Jan. 30, 2025 (GLOBE NEWSWIRE) -- Jupiter Neurosciences, Inc. (NASDAQ: JUNS) (“Jupiter” or the “Company”), a clinical-stage pharmaceutical company developing JOTROL™, a patented resveratrol-based platform, today announced a strategic partnership with Zina Biopharmaceuticals, LLC ("Zina") to support all aspects of Jupiter’s upcoming Phase 2a clinical trial for Parkinson’s disease. 

 Jupiter Neurosciences (JUNS) conducted a Phase I study demonstrating that JOTROL achieves over nine times higher bioavailability compared to resveratrol used in earlier clinical trials (e.g., Turner et al., MCI/Early Alzheimer’s Disease trial, and Yui et al., Friedreich’s Ataxia trial). The results of this Phase I study, which will be cross-referenced in all upcoming JOTROL trials, were published in the Journal of Alzheimer’s Disease and AAPS Open in February 2022.