Related Experiment Video
Updated: Sep 4, 2025
In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Moxifloxacin rescues SMA phenotypes in patient-derived cells and animal model
Camille Januel1, Giovanna Menduti2, Kamel Mamchaoui3
1INSERM/UEVE, UMR 861, Université Paris Saclay, I-STEM, AFM-Telethon, Rue Henri Desbruères, 91100, Corbeil-Essonnes, France.
Abstract:
Spinal muscular atrophy (SMA) is a genetic disease resulting in the loss of α-motoneurons followed by muscle atrophy. It is caused by knock-out mutations in the survival of motor neuron 1 (SMN1) gene, which has an unaffected, but due to preferential exon 7 skipping, only partially functional human-specific SMN2 copy. We previously described a Drosophila-based screening of FDA-approved drugs that led us to discover moxifloxacin. We showed its positive effect on the SMN2 exon 7 splicing in SMA patient-derived skin cells and its ability to increase the SMN protein level. Here, we focus on moxifloxacin's therapeutic potential in additional SMA cellular and animal models. We demonstrate that moxifloxacin rescues the SMA-related molecular and phenotypical defects in muscle cells and motoneurons by improving the SMN2 splicing. The consequent increase of SMN levels was higher than in case of risdiplam, a potent exon 7 splicing modifier, and exceeded the threshold necessary for a survival improvement. We also demonstrate that daily subcutaneous injections of moxifloxacin in a severe SMA murine model reduces its characteristic neuroinflammation and increases the SMN levels in various tissues, leading to improved motor skills and extended lifespan. We show that moxifloxacin, originally used as an antibiotic, can be potentially repositioned for the SMA treatment.
Insights
Moxifloxacin, an antibiotic, shows promise for treating spinal muscular atrophy (SMA). It improves SMN2 splicing, boosts SMN protein levels, and enhances motor function and survival in SMA models.
Area of Science:
- Neurology
- Genetics
- Pharmacology
Background:
- Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by mutations in the SMN1 gene.
- A partially functional SMN2 gene copy in SMA patients leads to reduced survival motor neuron (SMN) protein levels.
- Previous research identified moxifloxacin as a potential therapeutic agent through a Drosophila-based drug screening.
Purpose of the Study:
- To evaluate the therapeutic potential of moxifloxacin in additional SMA cellular and animal models.
- To investigate moxifloxacin's effects on SMN2 splicing and SMN protein levels.
- To compare moxifloxacin's efficacy with risdiplam, a known splicing modifier.
Main Methods:
- Testing moxifloxacin in SMA patient-derived cells and SMA murine models.
- Assessing SMN2 exon 7 splicing and SMN protein levels.
- Evaluating molecular and phenotypical defects, neuroinflammation, motor skills, and lifespan in animal models.
Main Results:
- Moxifloxacin rescued SMA-related defects in muscle cells and motoneurons by enhancing SMN2 splicing.
- Moxifloxacin increased SMN levels more effectively than risdiplam, exceeding the survival-improving threshold.
- In SMA mice, moxifloxacin reduced neuroinflammation, increased SMN levels, improved motor function, and extended lifespan.
Conclusions:
- Moxifloxacin demonstrates significant therapeutic potential for SMA by improving SMN2 splicing and increasing SMN protein.
- Moxifloxacin offers a promising drug repositioning strategy for SMA treatment.
- The study highlights moxifloxacin's ability to address key molecular and phenotypical aspects of SMA.
