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.