# Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy

## TL;DR

Ergothioneine, an antioxidant, improves survival and motor function in a mouse model of spinal muscular atrophy by reducing mitochondrial dysfunction.

## Contribution

This study shows that prenatal ergothioneine supplementation can enhance SMA pup outcomes through mitophagy stimulation.

## Key findings

- ERGO improved survival and locomotor abilities of SMA pups.
- ERGO stimulated mitophagy in isolated diaphragm muscle.
- Prenatal ERGO treatment showed positive effects on SMA mouse models.

## Abstract

Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons. The conventional therapy does not always lead to a full restoration of the clinical symptoms, partially due to the need for early treatment. Accumulating evidence describes the crucial role of mitochondrial dysfunction and oxidative stress in skeletal muscle of SMA patients. We aimed to investigate the effects of prenatal supplementation with the antioxidant molecule ergothioneine (ERGO) on an SMNΔ7 mouse model of SMA containing a knockout of survival motor neuron protein (SMN1) and two transgenes, one with a single normal copy of human SMN2 and the second with a human SMN2 promoter and a human SMN2 cDNA lacking exon 7. ERGO had a significant positive effect on the survival and locomotor abilities of SMA pups. In isolated diaphragm muscle, ERGO was found to stimulate mitophagy. The results of the current study highlight the need for further research into ERGO as an adjuvant therapy for SMA.

Impact statementOur finding that ergothioneine supplementation improves survival in a murine model of spinal muscular atrophy may aid research into a novel potential adjuvant to alleviate the symptoms of this serious neuromuscular disease in humans.

Our finding that ergothioneine supplementation improves survival in a murine model of spinal muscular atrophy may aid research into a novel potential adjuvant to alleviate the symptoms of this serious neuromuscular disease in humans.

Spinal muscular atrophy (SMA) is a genetic disease affecting motor neurons. Individuals with SMA experience mitochondrial dysfunction and oxidative stress. The aim of the study was to investigate the effect of an antioxidant and neuroprotective substance, ergothioneine (ERGO), on an SMNΔ7 mouse model of SMA. The treatment of pregnant mice with ERGO improved the survival and motor function of SMA pups.