A new study has confirmed that moxifloxacin, a fluoroquinolone antibiotic, can increase the survival of motor neuron (SMN) protein levels in human cells and an animal model of spinal muscular atrophy (SMA).

The study, published in Cellular and Molecular Life Sciences, also showed that daily injections of moxifloxacin in a murine model lead to improved motor skills and more prolonged survival.

“Our previous research reported moxifloxacin, a fluoroquinolone antibiotic, to be an effective SMN2 Ex7 splicing booster in SMA patient fibroblasts,” the authors wrote.


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“This paper investigates moxifloxacin’s effect on the SMA molecular and phenotypical hallmarks in [motor neurons] generated from patient-derived induced pluripotent stem cells and a human in vitro model of neuromuscular junctions [NMJs], and in a severe SMA murine model, further reinforcing its therapeutic potential.”

The research team generated human-induced spinal motor neurons and obtained human primary and immortalized nonaffected and SMA myoblasts for the human cell studies, and they employed 64 delta 7 SMA mice for the in vivo murine model of SMA.

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The human cells were treated with the various drug compounds every 3 days for 10 days, after which cell viability was quantified and mRNA expression of SMN was determined. The mice were divided into 2 groups: vehicle and moxifloxacin hydrochloride and were injected daily, followed by weight assessments and motor performance testing daily. After sacrifice, the team performed immunohistochemical analyses and motor neuron counting on the murine tissues.

The results showed that moxifloxacin increased SMN levels and almost completely restored SMA motor neuron degeneration in the human cells, to a greater degree than risdiplam, the current first-line therapy in SMA. In the SMA mice, moxifloxacin significantly increased SMN protein levels in both the spinal cord and skeletal muscles.

Neurodegeneration was delayed and muscle trophism improved. The authors propose moxifloxacin as a possible treatment for SMA, and they suggest that drug repositioning of existing medications could be a valuable and rapid strategy for identifying new therapies for rare diseases.  

Reference

Januel C, Menduti G, Mamchaoui K, et al. Moxifloxacin rescues SMA phenotypes in patient-derived cells and animal model. Cell Mol Life Sci. Published online July 22, 2022. doi:10.1007/s00018-022-04450-8