Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1G93A mice

Journal of Nanobiotechnology, 2024 · DOI: https://doi.org/10.1186/s12951-024-02764-2 · Published: August 12, 2024

Simple Explanation

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no effective treatments. This study explores using mesenchymal stem cell–derived small extracellular vesicles (sEVs) delivered through the nose as a potential therapy for ALS. The study found that sEVs, when given through the nose, can reach the central nervous system in mice, specifically targeting spinal neurons and microglia. This delivery method led to improvements in motor skills and longer survival times in mice with ALS. The improvements were linked to reduced pathological changes usually seen in ALS, such as nerve cell death, synapse loss, axon damage, and inflammation in the spinal cord. The treatment appears to work by controlling inflammation and key signaling pathways that contribute to the disease.

Study Duration

1 Month

Participants

SOD1G93A transgenic mice and wildtype (WT) mice (C57BL/6J)

Evidence Level

Not specified

Key Findings

1
Intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia.
2
SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time.
3
Intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway

Research Summary

This study investigated the therapeutic potential of intranasal administration of mesenchymal stem cell-derived small extracellular vesicles (sEVs) in treating amyotrophic lateral sclerosis (ALS) using SOD1G93A mice. The results demonstrated that sEVs effectively reached the central nervous system, leading to improved motor function, prolonged survival time, and alleviation of pathological changes associated with ALS, such as motoneuron death and neuroinflammation. The study suggests that intranasal administration of sEVs is a promising therapeutic strategy for ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathways.

Practical Implications

Novel Therapeutic Strategy

Intranasal delivery of sEVs presents a non-invasive method for delivering treatment to the CNS, overcoming the challenges posed by the blood-brain barrier.

Potential for ALS Treatment

The study provides evidence for the potential use of sEVs as a therapeutic intervention for ALS, warranting further research and clinical trials.

Targeting Neuroinflammation

sEVs could be engineered to specifically target and modulate neuroinflammation in ALS and other neurodegenerative diseases.

Study Limitations

1
The components in sEVs and their detailed functional mechanisms have not been decoded in the present work.
2
therapeutic effects of sEVs should be combinatory because they contain diverse contents
3
we started sEV administration at the symptom onset of ALS in mutant mice and did not study whether sEV administration was also effective at the later stage of ALS.

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