PMID- 35477657
OWN - NLM
STAT- MEDLINE
DCOM- 20220808
LR  - 20230804
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 30
IP  - 8
DP  - 2022 Aug 3
TI  - Boosting the peripheral immune response in the skeletal muscles improved motor 
      function in ALS transgenic mice.
PG  - 2760-2784
LID - S1525-0016(22)00248-9 [pii]
LID - 10.1016/j.ymthe.2022.04.018 [doi]
AB  - Monocyte chemoattractant protein-1 (MCP1) is one of the most powerful 
      pro-inflammatory chemokines. However, its signaling is pivotal in driving injured 
      axon and muscle regeneration. We previously reported that MCP1 is more strongly 
      upregulated in the nervous system of slow-progressing than fast-progressing 
      SOD1(G93A) mice, the latter showing a poor immune response and eventual massive 
      nerve and muscle degeneration. To assess the MCP1-mediated therapeutic role, we 
      boosted the chemokine along the motor unit of the two SOD1(G93A) models through a 
      single intramuscular injection of a scAAV9 vector engineered with the Mcp1 gene. 
      We provided direct evidence underlying the pivotal role of the immune response in 
      driving skeletal muscle regeneration and thus the speed of ALS progression. The 
      comparative study performed in fast- and slow-progressing SOD1(G93A) mice 
      spotlights the nature and temporal activation of the inflammatory response as 
      limiting factors to preserve the periphery and interfere with the disease course. 
      In addition, we recorded a novel pleiotropic role of MCP1 in promoting peripheral 
      axon regeneration and modulating neuroinflammation, ultimately preventing 
      neurodegeneration. Altogether, these observations highlight the immune response 
      as a key determinant for disease variability and proffer a reasonable explanation 
      for the failure of systemic immunomodulatory treatments, suggesting new potential 
      strategies to hamper ALS progression.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Trolese, Maria Chiara
AU  - Trolese MC
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Scarpa, Carlotta
AU  - Scarpa C
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Melfi, Valentina
AU  - Melfi V
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Fabbrizio, Paola
AU  - Fabbrizio P
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Sironi, Francesca
AU  - Sironi F
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Rossi, Martina
AU  - Rossi M
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy.
FAU - Bendotti, Caterina
AU  - Bendotti C
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy. Electronic address: caterina.bendotti@marionegri.it.
FAU - Nardo, Giovanni
AU  - Nardo G
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di 
      Ricerche Farmacologiche Mario Negri Mario Negri IRCCS, Via Mario Negri 2, 20156 
      Milan, Italy. Electronic address: giovanni.nardo@marionegri.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220427
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - *Amyotrophic Lateral Sclerosis/genetics/therapy
MH  - Animals
MH  - Axons
MH  - Disease Models, Animal
MH  - Immunity
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal
MH  - Nerve Regeneration
MH  - Superoxide Dismutase/genetics
MH  - Superoxide Dismutase-1/genetics
PMC - PMC9372324
OTO - NOTNLM
OT  - amyotrophic lateral sclerosis
OT  - immune cells
OT  - motor neuron
OT  - mouse models
OT  - myogenesis
OT  - satellite cells
OT  - skeletal muscle
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/04/29 06:00
MHDA- 2022/08/09 06:00
PMCR- 2023/08/03
CRDT- 2022/04/28 05:22
PHST- 2021/10/19 00:00 [received]
PHST- 2022/04/15 00:00 [revised]
PHST- 2022/04/25 00:00 [accepted]
PHST- 2022/04/29 06:00 [pubmed]
PHST- 2022/08/09 06:00 [medline]
PHST- 2022/04/28 05:22 [entrez]
PHST- 2023/08/03 00:00 [pmc-release]
AID - S1525-0016(22)00248-9 [pii]
AID - 10.1016/j.ymthe.2022.04.018 [doi]
PST - ppublish
SO  - Mol Ther. 2022 Aug 3;30(8):2760-2784. doi: 10.1016/j.ymthe.2022.04.018. Epub 2022 
      Apr 27.