A novel drug therapy for recurrent laryngeal nerve injury using T-588.
OBJECTIVE
We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models.


METHODS
Animal study.


METHODS
Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold.


RESULTS
T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls.


CONCLUSIONS
These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.
Mori
Yuko
Y
Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Shiotani
Akihiro
A
Saito
Koichiro
K
Araki
Koji
K
Ikeda
Ken
K
Nakagawa
Masaya
M
Watabe
Kazuhiko
K
Ogawa
Kaoru
K
D000818:Animals; D004048:Diethylamines / Q000494:pharmacology / Q000627:therapeutic use*; D004576:Electromyography; D007821:Laryngeal Muscles / Q000187:drug effects / Q000294:innervation; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014826:Vocal Cord Paralysis / Q000188:drug therapy* / Q000473:pathology*
D004048:Diethylamines; D018696:Neuroprotective Agents; D013876:Thiophenes; C082372:T 588