In vivo gene therapy: A strategy for mutations, degenerations, and tumors

Tao Wang, Mingyang Yu, Ping Liu, Zhiqiang Song, Cheng Li, Jianmin Yang, Na Liu, In vivo gene therapy: A strategy for mutations, degenerations, and tumors, Genes & Diseases, 2025, 101808, ISSN 2352-3042, doi:10.1016/j.gendis.2025.101808. 

 The current review summarizes the development of DNA nucleases and delivery vectors for in vivo gene therapy, emphasizing recent progress.

Spatial perspective taking is impaired in spinocerebellar ataxias and Friedreich ataxia

Karamazovova, S., Laczó, M., Matuskova, V. et al. Spatial perspective taking is impaired in spinocerebellar ataxias and Friedreich ataxia. Sci Rep 15, 31126 (2025). doi:10.1038/s41598-025-16302-z 

This study aimed to investigate perspective taking in patients with SCA and Friedreich ataxia (FRDA) using two tests. The Perspective-Taking/Spatial Orientation Test (PTSOT) was administered to 30 SCA patients, 30 FRDA patients, and 34 healthy controls (HC). In addition, SCA and HC completed the Directional-approach Task and a comprehensive neuropsychological assessment. SCA patients performed significantly worse than HC on both perspective taking tests. FRDA patients performed better than SCA and differed from HC only in a subset of PTSOT measures. Perspective taking performance in SCA was associated with global cognition and multiple cognitive domains but not with cerebellar motor impairment.

Alpha–lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia

Talaverón-Rey, M., Reche-López, D., Povea-Cabello, S. et al. Alpha–lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia. Orphanet J Rare Dis 20, 453 (2025).doi:10.1186/s13023-025-03990-z 

 Treatment with ALA was able to correct partially the pathological alterations in mutant fibroblasts. The optimal ALA concentration was dependent on the number of expanded GAA triplet repeats in the FXN gene. The positive effect of ALA was also confirmed in induced neurons derived from FRDA mutant fibroblasts. Our results also suggest that the positive effect of ALA was mediated by Peroxisome Proliferator-Activated Receptor Gamma activation. 

Conclusions: Our results suggest that ALA treatment can increase the expression levels of frataxin and reverse the mutant phenotype in cellular models of FRDA.