Article

A novel drug therapy for recurrent laryngeal nerve injury using T-588.

Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
The Laryngoscope (impact factor: 1.75). 08/2007; 117(7):1313-8. DOI:10.1097/MLG.0b013e31805f681f pp.1313-8
Source: PubMed

ABSTRACT 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.
Animal study.
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.
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.
These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.

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Keywords

brain-derived neurotrophic factor
 
choline acetyltransferase immunoreactivity
 
common clinical therapy
 
glial cell line-derived neurotrophic factor
 
Insulin-like growth factor
 
ipsilateral nucleus ambiguus
 
motoneuron cell
 
motoneuron loss
 
motor nerve conduction velocity
 
neural cells
 
neurofunctional recovery
 
neuroprotective effects
 
new drug treatments
 
oral administration
 
peripheral nerve injury
 
recurrent laryngeal nerve
 
Significant improvements
 
synthetic compound
 
T-588 administration
 
treatment group