Spinal muscular atrophy:From approved therapies to future therapeutic targets for personalized medicine
| Autor: | Thomas H. Gillingwater, Helena Chaytow, Yu-Ting Huang, Kiterie M. E. Faller |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Genetic enhancement
RNA Splicing Disease Review Bioinformatics ubiquitination Neuroprotection General Biochemistry Genetics and Molecular Biology Muscular Atrophy Spinal Preclinical research medicine Animals Humans Molecular Targeted Therapy Precision Medicine neuromuscular junction business.industry apoptosis SMN Complex Proteins cytoskeleton Spinal muscular atrophy Motor neuron medicine.disease SMA gene therapy SMN medicine.anatomical_structure splicing modulator Gene Targeting neuroprotection Personalized medicine business |
| Zdroj: | Chaytow, H, Faller, K, Huang, Y & Gillingwater, T H 2021, ' Spinal muscular atrophy : From approved therapies to future therapeutic targets for personalized medicine ', Cell Reports Medicine, vol. 2, no. 7, 100346 . https://doi.org/10.1016/j.xcrm.2021.100346 Cell Reports Medicine |
| Popis: | Summary Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease that, in the most severe cases and when left untreated, leads to death within the first two years of life. Recent therapeutic advances have given hope to families and patients by compensating for the deficiency in survival motor neuron (SMN) protein via gene therapy or other genetic manipulation. However, it is now apparent that none of these therapies will cure SMA alone. In this review, we discuss the three currently licensed therapies for SMA, briefly highlighting their respective advantages and disadvantages, before considering alternative approaches to increasing SMN protein levels. We then explore recent preclinical research that is identifying and targeting dysregulated pathways secondary to, or independent of, SMN deficiency that may provide adjunctive opportunities for SMA. These additional therapies are likely to be key for the development of treatments that are effective across the lifespan of SMA patients. Graphical abstract Highlights Three licensed SMA therapies increase SMN levels, but are not a cure Other strategies to increase SMN levels are still under development Alternatives target the correction of dysregulated pathways following SMN loss Ultimately, a range of therapies may allow for a tailored treatment Spinal muscular atrophy, a childhood neurodegenerative disorder, is caused by survival motor neuron (SMN) protein loss. Chaytow et al. review the newly licensed therapies and their limitations, before discussing alternative targets to correct the numerous consequences of SMN loss. Ultimately, a range of therapies may become available, allowing for tailored treatment. |
| Databáze: | OpenAIRE |
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