PMC

Week 12 mean percentage change from baseline in MC lesion count by week 2 BOTE status. Percentage change from baseline in lesion count at week 12 was compared on the basis of the week 2 BOTE status (). In the vehicle-treated group, the mean percentage lesion count reduction at week 12 was 13.6% for BOTE– patients (n = 115; 54.2%) compared with 49.4% for BOTE+ patients (n = 97; 45.8%) at week 2. In the SB206-treated group, the mean percentage lesion count reduction at week 12 was 38.2% for BOTE– patients (n = 164; 42.1%) and 61.4% for BOTE+ patients (n = 226; 57.9%) at week 2. The magnitude of the percentage reduction from baseline in MC counts at week 12 was greater for patients who were BOTE+ at week 2 in both groups but highest in the SB206-treated group, regardless of week 2 BOTE status. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.

LS mean percentage change from baseline in MC lesion count over time by baseline BOTE score for integrated ITT population. Vehicle-treated baseline BOTE+ patients showed a greater reduction in lesion count than vehicle-treated baseline BOTE– patients. Over time, patients treated with SB206 showed a greater reduction in lesion count than those treated with vehicle regardless of BOTE status at baseline, whereas SB206-treated patients who were BOTE+ at baseline showed a greater reduction in lesion count than SB206-treated patients who were BOTE– at baseline. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.

Cleavage of SNAP23 with botulinum neurotoxin E (BotE) blocks cAMP-stimulated renin release. A: representative Western blot showing the effect of incubating intact JG cells with either vehicle (lane 1) or BotE (lane 2) on SNAP23. Note that cleaved SNAP23 with BotE is observed as a decrease on the 23-kDa band intensity, since the COOH-terminal portion recognized by the antibody is removed by BotE. The cleaved ∼26-aa fragment of SNAP23 (∼3 kDa) runs out of the gel and it is not detected. After treatment, JG cells were lysed and SDS-resolved in 12% polyacrylamide gels as described in materials and methods. Membranes were reblotted with an antibody against GAPDH as an internal loading control (∼35 kDa). GAPDH values were not changed (P = N.S.). B: optical density quantitation from SNAP23 before (vehicle) and after (60 nM BotE) treatment. Vehicle-treated O.D. values were arbitrarily set to 1 and the means ± SE of at least 7 independent experiments were determined (*P < 0.05). C: effect of SNAP23 cleavage with BotE on cAMP-stimulated renin release. The protocol described for A was repeated for secretion studies. JG cells were pretreated with either vehicle or BotE for 19 h. Graph shows stimulated renin release (F/IBMX-stimulated renin release − vehicle-treated renin release) expressed as percentage of renin content. Black bar is JG cells in the absence of BotE (n = 7). Gray bars are JG cells pretreated with 10 (n = 7, *P < 0.02 vs. black bar) or 60 nM BotE (n = 10, #P < 0.03 vs. black bar). Striped gray bar represents JG cells pretreated with boiled/inactive BotE as a control. Basal renin release values were not significantly different: No-BotE = 2.0 ± 0.3; 10 nM BotE = 3.3 ± 0.7; 60 nM Bot E = 4.6 ± 0.7 (P = N.S.).

Week 12 mean percentage change in MC lesion count by maximum postbaseline BOTE status. Percentage change in lesion counts between baseline and week 12 was compared by the highest postbaseline BOTE status at any visit. In the vehicle-treated group, there was a 22.0% mean percentage reduction from baseline in lesion counts for patients who were BOTE– after baseline (n = 59; 27.4%), compared with a 33.8% mean reduction for patients with any detectable postbaseline BOTE inflammation (n = 156; 72.6%). In the SB206-treated group, these mean percentage reductions and patient numbers were 39.6% (n = 72; 18.1%) and 54.9% (n = 325; 81.9%) for BOTE– and BOTE+ patients, respectively. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.