Positive Interim Phase 1/2 Data for LX2006 in Friedreich Ataxia Cardiomyopathy Supporting Advancement to Registrational Study

NEW YORK, April 07, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today announced positive interim data across all dose cohorts of LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy. In both the Lexeo-sponsored SUNRISE-FA Phase 1/2 clinical trial (NCT05445323) and the Weill Cornell Medicine investigator-initiated Phase 1A trial (NCT05302271), treatment with LX2006 was associated with clinically significant improvements in cardiac biomarkers and functional measures, and increased frataxin protein expression was observed in all participants with cardiac biopsies.

Case Report: Complex Cardiac Arrhythmia Management in the ICU for an Adolescent with Friedreich Ataxia

Oluwatomini A Fashina, Stephen J Gleich, Derek N Opp, Yves Ouellette, Yu Kawai; Front. Pediatr. Sec. Pediatric Critical Care Volume 13 - 2025 | doi: 10.3389/fped.2025.1542513 

Despite optimization with dofetilide and metoprolol, he was readmitted with recurrent atrial arrhythmias and cardiogenic shock, secondary to probable amiodarone-induced thyrotoxicosis, requiring extracorporeal membrane oxygenation. His clinical course involved multisystem complications, prolonged hospitalization, and disease progression, with no recovery in systolic function despite control of his arrhythmia burden.Intensivists should be cognizant of multi-system complications that can arise when treating refractory cardiac arrhythmias, especially in those with concomitant genetic conditions.

Dietary and Lifestyle Interventions for the Management of Hereditary Ataxias

Wenyao Yang, Bruce Thompson, Faith Kwa; Front. Nutr. Sec. Nutrition and Metabolism Volume 12 - 2025, doi: 10.3389/fnut.2025.1548821

Currently, available options for HA primarily focus on symptomatic management, highlighting a critical need for complementary therapeutic strategies, such as dietary and lifestyle interventions. This review explains recent findings on dietary and nutraceutical interventions, as well as lifestyle modifications such as exercise and rehabilitation programs for HA. It outlines common types of HA, including Friedreich ataxia, spinocerebellar ataxias, ataxia with vitamin E deficiency, ataxia-telangiectasia, and studies on a mixed cohort of patients with HA.

Friedreich’s ataxia treatment’s sexual dimorphism

Ferreira, J. Friedreich’s ataxia treatment’s sexual dimorphism. Lab Anim 54, 75 (2025). doi:10.1038/s41684-025-01535-2 

While NRF2 activation was confirmed in males, no motor or sensory improvements were observed compared to wildtype animals. Female TG+ mice showed no response to the drugs, revealing sexual dimorphism in NRF2 signaling. These results identify early sexual dimorphism in response to treatment and highlight the limitations of NRF2 therapies in the TG+ model and the need for refined approaches in FA treatment development.

Larimar Therapeutics Provides Nomlabofusp Development Update and Reports Fourth Quarter and Full Year 2024 Financial Results

BALA CYNWYD, Pa., March 24, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) Potential for Accelerated Approval Pathway Based on FXN Concentrations as a Reasonably Likely Surrogate Endpoint (RSLE): FDA stated in written correspondence associated with a meeting through the START pilot program that they are open to considering the use of FXN concentration as a RLSE and the acceptability of FXN’s use as an RLSE would ultimately be a matter of review of the data in a future marketing application.

Increases in Skin FXN as Evidence of Effectiveness: FDA recommended focusing on assessments of skin FXN concentrations rather than buccal FXN concentrations due to more consistent sampling and less variability. FDA acknowledged that recently submitted data appear to support a relationship between increased FXN concentrations in skin cells and relevant tissues such as the heart, dorsal root ganglion and skeletal muscle. FDA also acknowledged that the nonclinical studies were performed at relevant human doses.

FDA also suggested that Larimar consider exploring the relationship between increases in FXN in skin and changes in pharmacodynamic markers such as lipid profiles and/or clinical measures to provide additional support for the use of FXN as a RLSE.

BLA Submission and Initiation of Global Phase 3 Study on Track: Larimar has obtained feedback from both FDA and EMA on the global Phase 3 study protocol and is on track to initiate the study by mid-2025 with potential sites in the U.S., Europe, U.K., Canada, and Australia. Larimar is targeting the BLA submission to seek accelerated approval by the end of 2025.

Comparative analysis of large language models on rare disease identification

Ao, G., Chen, M., Li, J. et al. Comparative analysis of large language models on rare disease identification. Orphanet J Rare Dis 20, 150 (2025). doi:10.1186/s13023-025-03656-w 

The LLMs performed better than human physicians, and Claude 3.5 Sonnet achieved the highest accuracy at 78.9%, significantly surpassing the accuracy of human physicians, which was 26.3%. These findings suggest that LLMs can improve rare disease diagnosis and serve as valuable tools in clinical settings, particularly in regions with limited resources. However, further validation and careful consideration of ethical and privacy issues are necessary for their effective integration into medical practice.

Early onset development of hypertrophic cardiomyopathy in less than 1 year in a patient with familial Friedrich's ataxia: Case report

Yasmine Ouaddouh, Salma Bouyaddid, Zakaria Bazid, Nabila Ismaili, Noha El Ouafi, Early onset development of hypertrophic cardiomyopathy in less than 1 year in a patient with familial Friedrich's ataxia: Case report, Radiology Case Reports, Volume 20, Issue 6, 2025, Pages 3016-3020, ISSN 1930-0433, doi:10.1016/j.radcr.2025.03.001. 

Friedreich's hypertrophic cardiomyopathy has been reported as the most significant cause of mortality, especially among younger patients with early onset disease manifestations.

Jupiter Neurosciences Inc. (JUNS) reports earnings

The report was filed on March 28, 2025. JOTROL is being developed for multiple indications including Parkinson’s Disease, Mild Cognitive Impairment/early Alzheimer’s Disease, and rare diseases such as Mucopolysaccharidoses Type 1, Friedreich’s ataxia, and MELAS.

Redox homeostasis and Inflammation in fibroblasts of patients with Friedreich Ataxia: a possible cross talk

Andrea Quatrana, Sara Petrillo Sara Petrillo, Caterina Torda Caterina Torda, Eleonora De Santis, Enrico Bertini Enrico Bertini, Fiorella Piemonte. Front. Mol. Neurosci., Sec. Molecular Signalling and Pathways, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1571402.

We found a significant activation of the TLR4/NF-kB/IL-1β axis in patients, associated to a consistent increase of the redox enzymes thioredoxin 1 (TRX1) and glutaredoxin 1 (GLRX1), which are essential to activate NF-kB under oxidative stress conditions. Furthermore, we investigated the role of 4-HNE, a by-product of lipid peroxidation, as a potential mediator between ferroptosis and inflammation in FRDA.

Systemic AAV Gene Therapy with Next Generation Engineered Capsids for Treatment of CNS and Cardiac Symptoms in Friedreich’s Ataxia

MDA Conference 2025. Ryan Kast, PhD, Capsida Biotherapeutics, Celeste Stephany, PhD, Capsida Biotherapeutics, Miguel Chuapoco, PhD, Capsida Biotherapeutics, Xiaojing Shi, PhD, Capsida Biotherapeutics, Assaf Beck, PhD, Capsida Biotherapeutics, Austin Kidder, Capsida Biotherapeutics, Yixi Wang, Capsida Biotherapeutics, Kevin Lam, Capsida Biotherapeutics, Nicholas Flytzanis, PhD, Capsida Biotherapeutics, Nick Goeden, PhD, Capsida Biotherapeutics. The engineered capsid delivering human FXN transduced more than 80% of cerebellar Purkinje cells, dentate nucleus neurons, motor neurons in the cortex and spinal cord, and nearly 30% of cardiac tissue area. FXN protein levels in treated NHPs were 8.2x higher than endogenous levels in the motor cortex and 1.7x in the heart as measured by ELISA. Moreover, substantial FXN RNA expression was detected in the retina (~1E6 copies/ug RNA) suggesting potential benefit for sensory vision loss experienced by FA patients. Significant de-targeting of the liver and other non-target tissues contributed to the favorable safety profile characterized by no adverse immunogenicity, clinical pathology, and histopathology findings.

LEXEO THERAPEUTICS REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS AND OPERATIONAL HIGHLIGHTS

NEW YORK, March 24, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. . 

Mid-Year Clinical Update Expected to Include: 

Safety and tolerability data for all participants dosed across both the SUNRISE-FA and Weill Cornell clinical trials (at least 16 participants, including 6 participants with abnormal LVMI at baseline) 

Pre- and post-treatment cardiac frataxin protein expression measured via LCMS for all four participants at the highest dose (1.2x1012 vg/kg, Cohort 3) 

Clinical biomarker data, including left ventricular mass index (LVMI), left ventricular wall thickness and high-sensitivity troponin I, for participants with >6-months of follow up 

Functional and patient-reported outcome data for participants with >6-months of follow up 

Safety: LX2006 continues to be generally well tolerated with no new treatment-related serious adverse events to report

Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study

Georgiou-Karistianis, N., Corben, L.A., Lock, E.F., Bujalka, H., Adanyeguh, I., Corti, M., Deelchand, D.K., Delatycki, M.B., Dogan, I., Farmer, J., França, M.C., Jr., Gabay, A.S., Gaetz, W., Harding, I.H., Joers, J., Lax, M.A., Li, J., Lynch, D.R., Mareci, T.H., Martinez, A.R.M., Pandolfo, M., Papoutsi, M., Parker, R.G., Reetz, K., Rezende, T.J.R., Roberts, T.P., Romanzetti, S., Rudko, D.A., Saha, S., Schulz, J.B., Subramony, S.H., Supramaniam, V.G., Lenglet, C. and Henry, P.-G. (2025), Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study. Ann Neurol. doi: 10.1002/ana.27237

 Our findings provide strong imaging evidence of impaired development of spinal cord and superior cerebellar peduncles during childhood in Friedreich ataxia and open the way for the use of neuroimaging biomarkers in clinical trials.

Debates over orphan drug pricing: a meta-narrative literature review

Hanchard, M.S. Debates over orphan drug pricing: a meta-narrative literature review. Orphanet J Rare Dis 20, 107 (2025). doi:10.1186/s13023-025-03634-2 

The review finds a sustained call for reform, centred on welfare economics and resource allocation, where current incentives and regulations are held to be insufficient. Overall, the article recommends that regulators look to alternative models of innovation steeped in social science thinking to modify reviewing appraisal, coverage, and reimbursement processes for orphan drugs. Also, that greater patient inclusion and transparency would help include a wider range of intangible social factors that rare disease patients face in accessing high priced orphan drugs.

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable

Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable. Front. Mol. Neurosci. Sec. Brain Disease Mechanisms, Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1511388 

These data show that decreased barrier integrity is a pathophysiologic phenotype of FA brain microvascular endothelial cells. Clinically, this may be a targetable pathway to abrogate brain iron accumulation, neuroinflammation, and neurodegeneration profiles of FA. Additionally, investigation into other barrier systems, such as the blood-nerve barrier, blood-CSF barrier, or cardiac vasculature may inform on extra-neural symptoms experienced by the FA patient.

SKYCLARYS™ (omaveloxolone) Approval by Health Canada Ushers in a New Era for Friedreich’s Ataxia Treatment in Canada

TORONTO, March 17, 2025 /CNW/ - Biogen Canada Inc. is pleased to announce that Health Canada has approved SKYCLARYS™ (omaveloxolone) for the treatment of Friedreich’s ataxia (FA) in patients 16 years of age and older.2 This approval – granted under Health Canada’s Priority Review process – marks an important milestone making SKYCLARYS the only treatment in Canada to specifically target the underlying mechanisms of this rare, progressive neurodegenerative disease.

P732: Identification of pathogenic expansions within FXN in individuals with suspected Friedreich ataxia diagnoses

P732: Identification of pathogenic expansions within FXN in individuals with suspected Friedreich ataxia diagnoses, Bohm, Kaitlynne et al., Genetics in Medicine Open, Volume 3, 103101 doi:10.1016/j.gimo.2025.103101 

Our PCR and NGS-based test designed to detect pathogenic GAA repeat expansions and sequence variants within the FXN gene was successful in providing 18 positive test results to individuals known to have, or suspected of having, Friedreich Ataxia. The FA Identified sponsored testing program has presented a unique opportunity to understand the milieu of clinical characteristics of individuals with a positive FA diagnosis, and the health care providers seeking such testing for their patients.

P356: Prediction of tissue frataxin levels with long term administration of nomlabofusp in adults with Friedreich’s ataxia using modeling and simulations

P356: Prediction of tissue frataxin levels with long term administration of nomlabofusp in adults with Friedreich’s ataxia using modeling and simulations, Clayton, Russell et al., Genetics in Medicine Open, Volume 3, 102321. doi: 10.1016/j.gimo.2025.102321 

Modeling and simulations using PK and PD data from short term studies can be used to predict a potential long term therapeutic dose. In the majority of patients with FRDA, daily administration of 50 mg nomlabofusp is predicted to result in skin frataxin concentrations that are ≥ 50% of concentrations observed in healthy controls.

P289: Disease characteristics and tissue frataxin concentrations in adults with Friedreich’s ataxia participating in nomlabofusp interventional studies

Russell Clayton, Mohamed Hamdani, Noreen Scherer,, P289: Disease characteristics and tissue frataxin concentrations in adults with Friedreich’s ataxia participating in nomlabofusp interventional studies, Genetics in Medicine Open, Volume 3, Supplement 2, 2025, 102254, ISSN 2949-7744, doi10.1016/j.gimo.2025.102254. 

Tissue frataxin concentration data from these studies are consistent with prior studies demonstrating that lower frataxin concentrations are associated with earlier onset of disease. The range of characteristics observed in the population of patients with FRDA participating in the nomlabofusp interventional studies is representative of the general FRDA adult population. Buccal and skin cell frataxin levels correlate with each other.

A Study to Learn More About the Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich's Ataxia Who Are Prescribed it for the First Time

ClinicalTrials.gov ID NCT06623890.  Last Update Posted 2025-03-04

In this study, researchers will learn more about the safety of BIIB141, also known as omaveloxolone or SKYCLARYS®. This is a drug available for doctors to prescribe for people with Friedreich's Ataxia, also known as FA. This is known as an "observational" study, which collects health information about study participants without changing their medical care. Participants for this study will be found using a group called the Friedreich's Ataxia Global Clinical Consortium (FA GCC). This is a group of study research centers that help provide clinical care for people with FA.

The primary objective of this study is to assess the long-term safety of omaveloxolone as prescribed to participants with FA in the real-world setting, including characterization of all drug-induced liver injury (DILI) and congestive heart failure (CHF) AEs. The secondary objective of this study is to capture the reasons and timing of omaveloxolone treatment interruptions, discontinuations, and drug overdose.

Design Therapeutics Highlights Progress Across Lead GeneTAC® Programs and Reports Fourth Quarter and Full Year 2024 Financial Results

CARLSBAD, Calif., March 10, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc.. Friedreich Ataxia (FA) Design has initiated dosing in a Phase 1 clinical trial in healthy volunteers in Australia to evaluate the safety and pharmacokinetics (PK) of single ascending doses of DT-216P2 via multiple routes of administration (intravenous infusion, subcutaneous infusion and subcutaneous injection). A Phase 1/2 multiple ascending dose (MAD) clinical trial to assess safety, PK and pharmacodynamics (PD) in FA patients is anticipated to begin in mid-2025. Data based on twelve weeks of DT-216P2 dosing in patients is anticipated in 2026.

Autosomal Recessive Ataxias in Northeast Brazil: A Regional Multicenter Case Series

Camelo-Filho, A.E., da Rosa, R.F., Lima, P.L.G.S.B. et al. Autosomal Recessive Ataxias in Northeast Brazil: A Regional Multicenter Case Series. Cerebellum 24, 59 (2025). Doi:10.1007/s12311-025-01814-1

Patients underwent clinical evaluations, including neurological examinations and functional assessments. Results: Friedreich’s ataxia (FRDA) was the most prevalent diagnosis, accounting for 12 cases (21%), followed by Ataxia-Telangiectasia (A-T) with (N = 9; 15.8%) and Niemann-Pick Disease Type C (NPC) (N = 9; 15.8%). Metabolic disorders, including Cerebrotendinous Xanthomatosis (N = 6;10.5%) were also common causes.

Design Therapeutics Highlights Progress Across Lead GeneTAC® Programs

CARLSBAD, Calif., March 10, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. today announced progress across its portfolio of GeneTAC® candidates and reported fourth quarter and full year 2024 financial results.

Friedreich Ataxia (FA) Design has initiated dosing in a Phase 1 clinical trial in healthy volunteers in Australia to evaluate the safety and pharmacokinetics (PK) of single ascending doses of DT-216P2 via multiple routes of administration (intravenous infusion, subcutaneous infusion and subcutaneous injection). A Phase 1/2 multiple ascending dose (MAD) clinical trial to assess safety, PK and pharmacodynamics (PD) in FA patients is anticipated to begin in mid-2025. Data based on twelve weeks of DT-216P2 dosing in patients is anticipated in 2026.

FDA Action Update, February 2025: Approvals, Designations, and Acceptances

NeurologyLive. March 9, 2025. The FDA was busy in March 2025, making a number of decisions on potential new therapeutic agents including granting approvals, acceptances, and designations.

- Solid Biosciences' SGT-212 gene therapy for Friedreich ataxia received FDA clearance, targeting neurologic and systemic manifestations via dual administration routes. 

-On the same day, February 19, the FDA accepted PTC Therapeutics’ new drug application (NDA) for its investigational agent vatiquinone as a treatment for patients with Friedreich ataxia (FA)

Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction

Claire B. Montgomery, Lili Salinas, Garrett P. Cox, Lauren E. Adcock, Tiffany Chang, Francisco Figueroa, Gino Cortopassi, Elena N. Dedkova; Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction. Dis Model Mech 2025; dmm.052128. doi: https://doi.org/10.1242/dmm.052128

 We developed a novel Salinas-Montgomery Ataxia Scale (SMAS) which allows for more comprehensive assessment versus a 4-part cerebellar ataxia scale. Despite validating multiple sensitive techniques, we did not see any benefits of NRF2-inducing therapies in any tests. This was exacerbated by the discovery of a sexual dimorphism in FXNKD mice, in which males show a more significant decline and better responsiveness to NRF2-inducing therapeutics.

Solid Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates

CHARLESTOWN, Mass., March 06, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. SGT-212 for Friedreich’s ataxia (FA) As announced on January 7, 2025, the FDA has cleared the IND for SGT-212 for the treatment of FA. SGT-212 is the first gene therapy candidate to utilize a dual route of administration to treat FA. The Company expects to initiate a first-in-human, open-label, Phase 1b clinical trial of SGT-212 in the second half of 2025. The trial is expected to enroll non-ambulatory and ambulatory adult participants living with FA across up to three cohorts and is designed to evaluate the safety and tolerability of concurrent systemic and bilateral IDN administration of SGT-212.

Gait Characteristics in People with Friedreich Ataxia: Daily Life versus Clinic Measures

Hannah L. Casey • Vrutangkumar V. Shah • Daniel Muzyka • James McNames • Mahmoud El-Gohary • Kristen Sowalsky • Delaram Safarpour • Patricia (Patty) Carlson-Kuhta • Christian Rummey • Fay B. Horak • Christopher M. Gomez, Front. Neurol. Sec. Movement Disorders, Volume 16 - 2025 | doi: 10.3389/fneur.2025.1544453 

Digital gait characteristics from inertial sensors are sensitive and specific for FRDA in both environments. However, different gait measures were more sensitive and specific during free-living versus prescribed gait, suggesting that in-clinic gait does not reflect daily life gait.

A global perspective on research advances and future challenges in Friedreich ataxia

Indelicato, E., Delatycki, M.B., Farmer, J. et al. A global perspective on research advances and future challenges in Friedreich ataxia. Nat Rev Neurol (2025). doi:10.1038/s41582-025-01065-y

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.

'Editorial: The Mechanistic Investigation and Emerging Therapies for Friedreich's Ataxia'

Yina Dong, Vijayendran Chandran, Elisabetta Soragni, David R Lynch, Front. Pharmacol. Sec. Neuropharmacology Volume 16 - 2025 doi:10.3389/fphar.2025.1560808

By integrating mechanistic insights with novel therapeutic approaches and outcome measures, this collection paves the way for more comprehensive and effective interventions for FRDA patients.

Larimar Therapeutics Announces Dosing of Adolescents in Nomlabofusp Pediatric Pharmacokinetic Run-In Study for Patients with Friedreich’s Ataxia

BALA CYNWYD, Pa., Jan. 23, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), today announced that dosing of adolescents 12-17 years old has started in the Company’s pediatric PK run-in study for patients with Friedreich’s ataxia (FA). 

 “Dosing adolescents is the first step in evaluating the safety and PK of nomlabofusp in pediatric patients with FA. We continue to enroll adolescents in our first cohort. This cohort will be followed by a second cohort of children 2-11 years old. We expect to transition both the adolescents and children into the ongoing OLE study after assessing safety and exposure data from each successive cohort,” said Dr. Rusty Clayton, Chief Medical Officer of Larimar. “We look forward to reporting long-term 50 mg data in adults from our OLE study, as well as available data from adolescents completing the pediatric PK run-in study, in mid- 2025.”

Hypoxia as a medicine

Robert S. Rogers, Vamsi K. Mootha. Hypoxia as a medicine. Science Translational Medicine 22 Jan 2025 Vol 17, Issue 782 DOI: 10.1126/scitranslmed.adr4049

Oxygen is essential for human life, yet a growing body of preclinical research is demonstrating that chronic continuous hypoxia can be beneficial in models of mitochondrial disease, autoimmunity, ischemia, and aging. This research is revealing exciting new and unexpected facets of oxygen biology, but translating these findings to patients poses major challenges, because hypoxia can be dangerous.

Solid Biosciences Receives FDA Fast Track Designation for SGT-212 Dual Route of Administration Gene Therapy for Friedreich’s Ataxia

CHARLESTOWN, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. today announced that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for SGT-212, the Company’s, AAV-based gene therapy candidate for the treatment of Friedreich’s ataxia (FA). SGT-212 will deliver the full-length frataxin gene via dual routes of administration incorporating intradentate nucleus (IDN) and intravenous (IV) infusions, designed to promote restoration of therapeutic levels of the frataxin protein to address neurologic, cardiac and systemic clinical manifestations of FA.

Friedreich ataxia: what can we learn from non-GAA repeat mutations?

Lynch DR, Shen M, Wilson RB. Friedreich ataxia: what can we learn from non-GAA repeat mutations? Neurodegener Dis Manag. 2025 Jan 15:1-10. doi: 10.1080/17582024.2025.2452147. Epub ahead of print. PMID: 39810561. 

 Compound heterozygote patients with one expanded GAA allele and a non-GAA repeat mutation can have subtle differences in phenotype from typical FRDA, including, in patients with selected missense mutations, both more severe features and less severe features in the same patient. In this review, we propose explanations for such phenotypes based on the potential for activities of frataxin other than enhancement of iron-sulfur cluster synthesis, as well as crucial future experiments for fully understanding the role of frataxin in cells.

Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study

Tranfa M, Costabile T, Pontillo G, Scaravilli A, Pane C, Brunetti A, Saccà F, Cocozza S. Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study. Cerebellum. 2025 Jan 14;24(2):30. doi: 10.1007/s12311-025-01785-3. PMID: 39808241; PMCID: PMC11732920. 

Graph analysis revealed regional intra-cerebellar FC changes in FRDA, marked by reduced functional centrality in cerebellar regions of the vermis and responsible for executive functions. These changes correlated with cognitive alterations, highlighting the role of the cerebellar cortex in the cognitive impairment observed in FRDA. In conclusion, our observations confirm that the cerebellum is involved in the pathophysiology of FRDA not only from a structural, but also from a functional standpoint, and suggests that integrating information from different parcellations could provide complementary knowledge and help us in decoding the exact relationship between FC alterations and cognitive changes in FRDA.

Life and death of Yfh1: how cool is cold denaturation

Temussi PA, Martin SR, Pastore A. Life and death of Yfh1: how cool is cold denaturation. Q Rev Biophys. 2025 Jan 13;58:e2. doi: 10.1017/S0033583524000180. PMID: 39801016. 

 The present review aims at recapitulating all the open questions that Yfh1 has helped to address, including understanding the differences and commonalities of the cold, heat and pressure unfolded states. This protein thus offers a unique tool for studying aspects of protein stability so far been considered difficult to assess and provides important guidelines that could allow the identification of other similar systems.

Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study

Lischewski SA, Konrad K, Dogan I, Didszun C, Costa AS, Schawohl SA, Giunti P, Parkinson MH, Mariotti C, Nanetti L, Durr A, Ewenczyk C, Boesch S, Nachbauer W, Klopstock T, Stendel C, de Rivera Garrido FJR, Schöls L, Fleszar Z, Klockgether T, Grobe-Einsler M, Giordano I, Rai M, Pandolfo M, Schulz JB, Reetz K; EFACTS study group. Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study. Eur J Neurol. 2025 Jan;32(1):e70011. doi: 10.1111/ene.70011. PMID: 39797559; PMCID: PMC11724196. 

Significant anthropometric abnormalities were identified, with underweight and short stature prevalent in children and overweight in adults. These findings highlight the need for regular nutritional monitoring and interventions to manage underweight in children and promote healthy weight in adults.

Effects of physiotherapy on degenerative cerebellar ataxia: a systematic review and meta-analysis

Matsugi A, Bando K, Kondo Y, Kikuchi Y, Miyata K, Hiramatsu Y, Yamanaka Y, Tanaka H, Okuda Y, Haruyama K and Yamasaki Y (2025) Effects of physiotherapy on degenerative cerebellar ataxia: a systematic review and meta-analysis. Front. Neurol. 15:1491142. doi: 10.3389/fneur.2024.1491142

Physical therapy, especially multi-aspect physical therapy such as muscle strengthening, coordination training, gait training, and ADL training, may reduce DCA symptoms. Further, balance and aerobic training can be added to the program. However, the estimated effect size may change in future studies because of the serious RoB, very low certainty of evidence, and high heterogeneity with SARA as the primary outcome. High-quality RCTs are required to establish evidence for the effectiveness of physical therapy in patients with DCA.

Poincaré plot analysis of ECG uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich’s ataxia

Poincaré plot analysis of ECG uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich’s ataxia, Figueroa, Francisco et al., Heart Rhythm, Volume 0, Issue 0. DOI: 10.1016/j.hrthm.2024.12.041

Our study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and ANS dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.

Capsida Announces AbbVie Opt-in for First Genetic Medicine Program from Neurodegenerative Disease Collaboration

THOUSAND OAKS, Calif., Jan. 7, 2025 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced that AbbVie has exercised an option for the first neurodegenerative disease program under their ongoing collaboration. Capsida will receive a $40 million license payment and is eligible for additional milestones and royalties.

Capsida's wholly owned pipeline includes a potential first-in-class treatment for STXBP1 developmental and epileptic encephalopathy, best-in-class treatment for Parkinson's disease associated with GBA mutations, and best-in-class therapy for Friedreich's ataxia. In addition to its wholly owned programs, the Company has validating partnerships with AbbVie, Lilly, and CRISPR Therapeutics.

Solid Biosciences Announces FDA IND Clearance for First-In-Industry Dual Route of Administration Gene Therapy to Treat Both Neurologic and Cardiac Manifestations of Friedreich’s Ataxia

CHARLESTOWN, Mass., Jan. 07, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SGT-212 for the treatment of Friedreich’s ataxia (FA). SGT-212 is the Company’s novel, AAV-based FA gene therapy candidate designed to deliver full-length frataxin via systemic intravenous (IV) infusion as well as direct intradentate nuclei (IDN) infusion into the cerebellum. SGT-212 is designed to treat the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression. 

In the second half of 2025, the Company expects to initiate a first-in-human, open-label, dose-finding Phase 1b clinical trial of SGT-212. The study will enroll non-ambulatory and ambulatory adult patients living with FA across up to three cohorts and will evaluate the safety and tolerability of contemporaneous systemic and bilateral IDN administration of SGT-212. Participants in the trial will be followed out to five years after receiving SGT-212.

Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease

Hisey JA, Masnovo C, Mirkin SM. Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease. NAR Mol Med. 2024 Dec 5;1(4):ugae024. doi: 10.1093/narmme/ugae024. PMID: 39723156; PMCID: PMC11667243. 

H-DNA-forming repeats have been implicated in four REDs: Friedreich's ataxia, GAA-FGF14-related ataxia, X-linked Dystonia Parkinsonism, and cerebellar ataxia, neuropathy and vestibular areflexia syndrome. In this review, we summarize H-DNA's discovery and characterization, evidence for its existence and function in vivo, and the field's current knowledge on its role in physiology and pathology.

Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia

Vo ATT, Khan U, Liopo AV, Mouli K, Olson KR, McHugh EA, Tour JM, Pooparayil Manoj M, Derry PJ, Kent TA. Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia. Nanomaterials (Basel). 2024 Dec 13;14(24):2007. doi: 10.3390/nano14242007. PMID: 39728543. 

We demonstrate that pleozymes increased overall protein persulfidation in cells from apparently healthy individuals and from individuals with the mitochondrial protein mutation responsible for Friedreich's ataxia. We further find that pleozymes specifically enhanced Keap1 persulfidation, with subsequent increased accumulation of Nrf2 and Nrf2's antioxidant targets.