Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS
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Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS. / Leyton-Jaimes, Marcel F.; Ivert, Patrik; Hoeber, Jan; Han, Yilin; Feiler, Adam; Zhou, Chunfang; Pankratova, Stanislava; Shoshan-Barmatz, Varda; Israelson, Adrian; Kozlova, Elena N.
In: Scientific Reports, Vol. 10, No. 1, 20675, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS
AU - Leyton-Jaimes, Marcel F.
AU - Ivert, Patrik
AU - Hoeber, Jan
AU - Han, Yilin
AU - Feiler, Adam
AU - Zhou, Chunfang
AU - Pankratova, Stanislava
AU - Shoshan-Barmatz, Varda
AU - Israelson, Adrian
AU - Kozlova, Elena N.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-020-77578-x
DO - 10.1038/s41598-020-77578-x
M3 - Journal article
C2 - 33244084
AN - SCOPUS:85096676629
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 20675
ER -
ID: 252680243