Related Experiment Video
Updated: Nov 28, 2025
A Silicosis Mouse Model Established by Repeated Inhalation of Crystalline Silica Dust
Published on: January 6, 2023
Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS
Marcel F Leyton-Jaimes1, Patrik Ivert2, Jan Hoeber2,3
1Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, 84105, Beer Sheva, Israel.
Abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurological disorder characterized by motor neuron (MN) death and muscle dysfunction leading to mean survival time after diagnosis of only 2-5 years. A potential ALS treatment is to delay the loss of MNs and disease progression by the delivery of trophic factors. Previously, we demonstrated that implanted mesoporous silica nanoparticles (MSPs) loaded with trophic factor peptide mimetics support survival and induce differentiation of co-implanted embryonic stem cell (ESC)-derived MNs. Here, we investigate whether MSP loaded with peptide mimetics of ciliary neurotrophic factor (Cintrofin), glial-derived neurotrophic factor (Gliafin), and vascular endothelial growth factor (Vefin1) injected into the cervical spinal cord of mutant SOD1 mice affect disease progression and extend survival. We also transplanted boundary cap neural crest stem cells (bNCSCs) which have been shown previously to have a positive effect on MN survival in vitro and in vivo. We show that mimetic-loaded MSPs and bNCSCs significantly delay disease progression and increase survival of mutant SOD1 mice, and also that empty particles significantly improve the condition of ALS mice. Our results suggest that intraspinal delivery of MSPs is a potential therapeutic approach for the treatment of ALS.
Insights
Mesoporous silica nanoparticles loaded with therapeutic peptides, and neural stem cells, significantly delay disease progression and extend survival in mouse models of amyotrophic lateral sclerosis (ALS). Even empty nanoparticles showed benefits for ALS mice.
Area of Science:
- Neuroscience
- Biomaterials Science
- Regenerative Medicine
Background:
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options.
- Motor neuron (MN) degeneration leads to progressive muscle dysfunction and paralysis.
- Trophic factors and stem cell therapies show promise for slowing ALS progression.
Purpose of the Study:
- To evaluate the therapeutic potential of mesoporous silica nanoparticles (MSNs) loaded with trophic factor mimetics for ALS treatment.
- To assess the efficacy of transplanted boundary cap neural crest stem cells (bNCSCs) in ALS mouse models.
- To investigate the impact of intraspinal delivery of these agents on disease progression and survival.
Main Methods:
- MSNs loaded with peptide mimetics of Cintrofin, Gliafin, and Vefin1 were prepared.
- These MSNs and bNCSCs were stereotactically injected into the cervical spinal cord of mutant SOD1 mice.
- Disease progression and survival rates were monitored in treated and control groups.
- The effects of empty MSNs were also evaluated.
Main Results:
- MSNs loaded with trophic factor mimetics significantly delayed disease progression and increased survival in mutant SOD1 mice.
- Transplanted bNCSCs also demonstrated a significant positive effect on disease progression and survival.
- Even empty MSNs showed a notable improvement in the condition of ALS mice.
- Intraspinal delivery of MSNs emerged as a promising therapeutic strategy.
Conclusions:
- Intraspinal delivery of MSNs loaded with trophic factor mimetics represents a viable therapeutic strategy for ALS.
- bNCSCs also show therapeutic potential for ALS treatment.
- Further research into MSN-based therapies could lead to effective treatments for neurodegenerative diseases like ALS.
