PMID- 34708585
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220531
IS  - 2190-6009 (Electronic)
IS  - 2190-5991 (Print)
IS  - 2190-5991 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Feb
TI  - Intramuscular tetanus neurotoxin reverses muscle atrophy: a randomized controlled 
      trial in dogs with spinal cord injury.
PG  - 443-453
LID - 10.1002/jcsm.12836 [doi]
AB  - BACKGROUND: Motor symptoms of spinal cord injury (SCI) considerably impair 
      quality of life and are associated with a high risk of secondary diseases. So 
      far, no pharmacological treatment is available for these symptoms. Therefore, we 
      conducted a randomized, double-blinded, placebo-controlled study in dogs with 
      spontaneous SCI due to disc herniation to test whether a reduction of spinal 
      inhibitory activity by intramuscular injections of tetanus neurotoxin (TeNT) 
      alleviates motor symptoms such as muscle atrophy or gait function. METHODS: To 
      this end, 25 dogs were treated with injections of either TeNT or placebo into 
      their paretic hindlimb muscles. Effects of TeNT on muscle thickness were assessed 
      by ultrasound, while effects on gait function were measured using the modified 
      functional scoring system in dogs. RESULTS: Four weeks after the TeNT injections, 
      muscle thickness of the gluteus medius muscle (before median 1.56 cm 
      [inter-quartile range IQR 1.34-1.71 cm] and after median 1.56 cm [IQR 
      1.37-1.85 cm], P-value 0.0133) as well as of the rectus femoris muscle (before 
      median 0.76 cm [IQR 0.60-0.98 cm] and after median 0.93 cm [IQR 0.65-1.05 cm], 
      P-value 0.0033) significantly increased in the TeNT group. However, there was no 
      difference in gait function between the TeNT and placebo groups. The treatment 
      was well tolerated by all dogs without any signs of generalized tetanus symptoms 
      or any spreading of effects beyond the lumbar level of the injected hindlimbs. 
      CONCLUSIONS: With regard to the beneficial effects on muscle thickness, 
      intramuscular injections of TeNT represent the first pharmacological approach 
      that focally reverses muscle atrophy in SCI. Moreover, the study data support the 
      safety of this treatment when TeNT is used at low dose.
CI  - (c) 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John 
      Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting 
      Disorders.
FAU - Kutschenko, Anna
AU  - Kutschenko A
AUID- ORCID: 0000-0002-8240-664X
AD  - Department of Neurology, University Medical Center, Gottingen, Germany.
FAU - Manig, Anja
AU  - Manig A
AUID- ORCID: 0000-0002-1182-0843
AD  - Department of Neurology, University Medical Center, Gottingen, Germany.
FAU - Monnich, Angelika
AU  - Monnich A
AD  - Department of Neurology, University Medical Center, Gottingen, Germany.
FAU - Bryl, Beatrice
AU  - Bryl B
AD  - Neurological Department, Medical Park Berlin Humboldtmuhle, Berlin, Germany.
FAU - Alexander, Cecile-Simone
AU  - Alexander CS
AD  - TierReha Alexander, Tierarztpraxis fur Rehabilitation, Berlin, Germany.
FAU - Deutschland, Martin
AU  - Deutschland M
AD  - Neurological Referral Veterinary Surgery, Berlin, Germany.
FAU - Hesse, Stefan
AU  - Hesse S
AD  - Neurological Department, Medical Park Berlin Humboldtmuhle, Berlin, Germany.
FAU - Liebetanz, David
AU  - Liebetanz D
AD  - Department of Neurology, University Medical Center, Gottingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211027
PL  - Germany
TA  - J Cachexia Sarcopenia Muscle
JT  - Journal of cachexia, sarcopenia and muscle
JID - 101552883
RN  - 0 (Tetanus Toxin)
RN  - 11032-48-7 (tetanospasmin)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Dogs
MH  - Metalloendopeptidases
MH  - Muscular Atrophy/drug therapy/etiology/veterinary
MH  - *Quality of Life
MH  - *Spinal Cord Injuries/complications/drug therapy/veterinary
MH  - Tetanus Toxin/pharmacology
PMC - PMC8818617
OTO - NOTNLM
OT  - Dogs
OT  - Muscle thickness
OT  - Paraparesis
OT  - Paraplegia
OT  - Spinal cord injury
OT  - Tetanus neurotoxin
COIS- None declared.
EDAT- 2021/10/29 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/02/01
CRDT- 2021/10/28 07:03
PHST- 2021/09/08 00:00 [revised]
PHST- 2021/04/20 00:00 [received]
PHST- 2021/09/19 00:00 [accepted]
PHST- 2021/10/29 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/10/28 07:03 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - JCSM12836 [pii]
AID - 10.1002/jcsm.12836 [doi]
PST - ppublish
SO  - J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):443-453. doi: 10.1002/jcsm.12836. 
      Epub 2021 Oct 27.