Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine DOI
Fabiola De Marchi, Ivan Lombardi, Alessandro Bombaci

et al.

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce, with riluzole and edaravone offering only limited benefits. The emergence regenerative medicine, including stem cell therapy, gene-based interventions, bioengineering strategies, presents a new frontier ALS treatment. This review is based on comprehensive literature search using PubMed, Scopus clinical trials databases the recent therapeutic advancements in ALS, giving particular focus to medicine. article includes coverage cell-based therapies, mesenchymal cells, neural induced pluripotent cells; all which may offer potential neuroprotective immunomodulatory effects. Gene particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, tofersen becoming first FDA-approved genetic therapy ALS. also covers emerging approaches such as extracellular vesicles, immune-modulating techniques, CRISPR-based gene editing cellular reprogramming, that hold promise altering disease progression. While medicine provides hope patients, significant challenges remain. Biomarkers will play crucial role guiding personalized treatment ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different strategies maximize patient outcomes. Although still its early stages, integration into paradigms could redefine management potentially alter natural course.

Language: Английский

TDP-43 dysregulation impairs cholesterol metabolism linked with myelination defects DOI Creative Commons
Irene García-Toledo, Juan M. Godoy-Corchuelo, Luis C. Fernández-Beltrán

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Abstract TDP-43 is a nuclear protein encoded by the TARDBP gene, which forms pathological aggregates in various neurodegenerative diseases, collectively known as proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These diseases are characterized multiple mechanisms, with disruptions lipid regulatory pathways emerging critical factor. However, role of regulation brain homeostasis potential connection dysfunction to myelin alterations proteionopathies remain poorly understood, despite fact that lipids, particularly cholesterol, comprise nearly 70% myelin. To investigate causal relationship between cholesterol homeostasis, we conducted multi-omics analyses (lipidomics, transcriptomics, functional splicing) on frontal cortex from TardbpM323K/M323K knock-in mouse model. Lipidomic analysis revealed related membrane composition droplet accumulation, affecting cholesterol-related species. We found higher droplets accumulation primary fibroblast derived these mice, well mutant mice. Similarly, immunohistochemical detection marker was post-mortem cortex, gray white matter, FTLD-TDP patients compared non-neurological controls. Transcriptomic showed pathology led transcriptional dysregulation genes essential for production maintenance. identified impaired metabolism, mainly through downregulation endogenous synthesis, alongside upregulated transport pathways, further replicated transcriptomic datasets. Collectively, our findings suggest disrupts potentially compromising integrity.

Language: Английский

Citations

0
Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mice DOI Creative Commons
Ali Rezaei,

Virág Kocsis-Jutka,

Zeynep I. Gunes

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Language: Английский

Citations

0
Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine DOI
Fabiola De Marchi, Ivan Lombardi, Alessandro Bombaci

et al.

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce, with riluzole and edaravone offering only limited benefits. The emergence regenerative medicine, including stem cell therapy, gene-based interventions, bioengineering strategies, presents a new frontier ALS treatment. This review is based on comprehensive literature search using PubMed, Scopus clinical trials databases the recent therapeutic advancements in ALS, giving particular focus to medicine. article includes coverage cell-based therapies, mesenchymal cells, neural induced pluripotent cells; all which may offer potential neuroprotective immunomodulatory effects. Gene particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, tofersen becoming first FDA-approved genetic therapy ALS. also covers emerging approaches such as extracellular vesicles, immune-modulating techniques, CRISPR-based gene editing cellular reprogramming, that hold promise altering disease progression. While medicine provides hope patients, significant challenges remain. Biomarkers will play crucial role guiding personalized treatment ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different strategies maximize patient outcomes. Although still its early stages, integration into paradigms could redefine management potentially alter natural course.

Language: Английский

Citations

0