Persistence of the synaptosomal-associated protein-25 cleavage product after intradetrusor botulinum toxin A injections in patients with myelomeningocele showing an inadequate response to treatment.
OBJECTIVE To monitor the presence and cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) by botulinum toxin type A (botox-A), in human detrusor muscle, as the effects of botox-A in the urinary bladder last significantly longer than when applied for disorders of striated muscles. PATIENTS AND METHODS Tissue samples were obtained from eight patients with end-stage neurogenic bladder at different times after injection with botox-A. The resected bladder domes were examined using biochemical and immunohistological techniques. RESULTS The presence of intact SNAP-25 in human bladder was detected, for the first time, in all samples by both Western blotting and immunofluorescence. By contrast, detection of a band potentially representing toxin-cleaved SNAP-25(A) required its enrichment by precipitation with a specific antibody. This putative product was present in four of six patients treated with botox-A 5 weeks to 11 months previously, but could not be detected in one patient 30 months after botox injection, and in an untreated control. Fluorescence microscopy showed no obvious effects of the toxin treatment on the presence and pattern of SNAP-25-positive neurones. CONCLUSIONS A limited amount of SNAP-25 appears to be cleaved in nerves that innervate the smooth detrusor muscle in most patients who had been injected with botox-A; its absolute identification was precluded by the sensitivity of the detection. This protein was detectable much longer after toxin treatment than published for rodent striated muscle, and thus could contribute to the clinically reported longer duration of the effectiveness of botox-A.
Schulte-Baukloh
Heinrich
H
Department of Urology, St. Hedwig Hospital, Charité Medical School, Humboldt University Berlin, Germany. hschultebaukloh@hotmail.com
Zurawski
Tomas H
TH
Knispel
Helmut H
HH
Miller
Kurt
K
Haferkamp
Axel
A
Dolly
J Oliver
JO
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008591:Meningomyelocele / Q000150:complications*; D009103:Multiple Sclerosis / Q000150:complications; D009130:Muscle, Smooth / Q000187:drug effects* / Q000473:pathology; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000473:pathology; D014563:Urodynamics