Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS.

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.

• Authors: Marcel F Leyton-Jaimes, Patrik Ivert, Jan Hoeber, Yilin Han, Adam Feiler, Chunfang Zhou, Stanislava Pankratova, Varda Shoshan-Barmatz, Adrian Israelson, Elena N Kozlova
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 20675 (11 26 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33244084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• Vascular Endothelial Growth Factor A
• Silicon Dioxide
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Amyotrophic Lateral Sclerosis (drug therapy, metabolism, pathology)
• Animals
• Cell Survival (drug effects)
• Cells, Cultured
• Cervical Cord (drug effects, metabolism, pathology)
• Disease Models, Animal
• Disease Progression
• Embryonic Stem Cells (drug effects, metabolism, pathology)
• Female
• Glial Cell Line-Derived Neurotrophic Factor (metabolism)
• Mice
• Motor Neurons (drug effects, metabolism, pathology)
• Neural Crest (drug effects, metabolism, pathology)
• Neural Stem Cells (drug effects, metabolism, pathology)
• Silicon Dioxide (pharmacology)
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1 (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)