In the human urothelium and suburothelium, intradetrusor botulinum neurotoxin type A does not induce apoptosis: preliminary results.
BACKGROUND
Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.


OBJECTIVE
To investigate BoNTA-induced apoptosis in patients with refractory neurogenic OAB.


METHODS
Twelve refractory OAB patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) and seven controls were included prospectively.


METHODS
The number of apoptotic cells before and 4 wk after first intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining.


CONCLUSIONS
Comparison of TUNEL-positive cells (yes vs no) in the bladder urothelium and suburothelium revealed no significant differences in OAB patients before (4 of 12, 33%) versus after (3 of 12, 25%) BoNTA treatment (p=0.99). In addition, no significant differences (p=0.99) were found in OAB patients versus controls. Because our findings are based on first intradetrusor BoNTA injections only, it is unclear whether the results could be extrapolated to repeat injections.


CONCLUSIONS
In contrast to preliminary animal experiments, first intradetrusor BoNTA injections for treating refractory neurogenic OAB--a highly effective treatment--did not induce apoptosis in the bladder urothelium and suburothelium.
Kessler
Thomas M
TM
Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and University College London Institute of Neurology, Queen Square, London, UK. tkessler@gmx.ch
Khan
Shahid
S
Panicker
Jalesh N
JN
Elneil
Sohier
S
Brandner
Sebastian
S
Fowler
Clare J
CJ
Roosen
Alexander
A
D000283:Administration, Intravesical; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000008:administration & dosage*; D011446:Prospective Studies; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000473:pathology*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000473:pathology*; D019459:Urothelium
D009498:Neurotoxins; D019274:Botulinum Toxins, Type A