Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00528 (Monit)
 35,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cervical dystonia (CD) is characterized by abnormal, involuntary contractions of the cervical and/or shoulder muscles. Direct injection of Botulinum toxin type A (BTX-A) into the affected muscles has been used successfully to treat this condition. However, clinical resistance to BTX-A therapy develops in a limited number of patients. Moreover, an unknown proportion of treated patients have a suboptimal response to their present therapy. BTX-B is antigenically distinct from BTX-A and possesses a different mechanism of action. Three randomized, double-blind, placebo-controlled clinical trials evaluated the safety and efficacy of BTX-B (Elan's BTX-B evaluated as NeuroBloc) as a treatment for patients with CD. Patients received a single dose of BTX-B ranging from 2,500 to 10,000 U. The primary efficacy evaluation for each of these studies used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. Additional efficacy measures included the TWSTRS severity, disability, and pain subscale scores, as well as the Patient Analog Pain Assessment and Patient's and Physician's Global Assessments of Change. In all three studies, groups receiving BTX-B displayed statistically significant improvements in TWSTRS total score and other efficacy end points compared with those who received placebo treatment. The clinical benefits after BTX-B treatment lasted 12 to 16 weeks and were observed in both BTX-A-responsive and BTX-A-resistant patients. In general, treatment with BTX-B was well tolerated and most of the reported adverse events were of short duration, mild to moderate in severity, and anticipated. The results from the three controlled clinical trials demonstrate the safety and efficacy of BTX-B in the treatment of patients with CD, including those who are resistant to BTX-A treatment.
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PMID:The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: summary of three controlled clinical trials. 1118 82

Recently, it was reported that botulinum toxin type B complex (BoNT/B) (NeuroBloc(R), Elan Pharmaceuticals) can produce an adequate therapeutic response in patients with antibody induced failure of botulinum toxin type A complex (BoNT/A) therapy. We wanted to study whether this effect is transient or sustained. For this, 10 consecutive patients (6 males, 4 females, age 54.6 +/- 14.3 years, duration of illness 15.8 +/- 7.0 years) with complete BoNT/A therapy failure and BoNT/A antibody titres in excess of 10mU/ml in the mouse diaphragm assay (MDA) received BoNT/B in an initial dose of 12370 +/- 1804MU. After the first BoNT/B application the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) improved from 20.1 +/- 3.0 to 11.9 +/- 3.4. In all patients systemic anticholinergic side effects occurred. Three patients had stable continuous responses to two, three and five subsequent BoNT/B applications. Six patients showed complete secondary therapy failure to the second or third subsequent BoNT/B applications. Side effects did no longer occur. In four of them the BoNT/B doses were doubled without producing any therapeutic benefit or any side effects. In five of them MDA testing was performed and revealed BoNT/B antibody titres in excess of 1mU/ml. One patient lost half of her initial BoNT/B responsiveness indicating partial secondary BoNT/B therapy failure. This partial therapy failure was seen on two consecutive application series and has not proceeded to complete therapy failure so far. BoNT/B seems to be only temporarily effective in the majority of patients with BoNT/A antibody induced therapy failure. Whether the formation of BoNT/B antibody points to a high antigenic potency of BoNT/B, to an increased immunoreactivity in BoNT/A antibody carriers or whether it is due to the large amount of protein applied in BoNT/B therapy needs to be studied.
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PMID:Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure. 1292 17

Botulinum toxin induced therapy failure type B antibody (BT-B, BT-B-AB) has so far only been reported after previous formation of antibodies against botulinum toxin type A (BT-A, BTA- AB). We wanted to explore the risk of BT-B-AB-induced therapy failure in patients who were exposed to botulinum toxin for the first time. For this purpose we followed nine patients with cervical dystonia receiving BT-B (NeuroBloc/Myo- Bloc, Elan Pharmaceuticals) in a dose of 11435 +/- 2977MU during 4.9 +/- 3.0 injection series. All patients showed a satisfactory initial therapeutic response as documented by a Toronto Western Spasmodic Torticollis Rating Scale score reduction from 17.7 +/- 9.4 to 5.3 +/- 4.8 and an overall subjective improvement of 56.1 +/- 28.3%. Seven patients experienced systemic anticholinergic side effects. Five patients had stable therapeutic responses over subsequent injection series. Four patients experienced complete therapy failure with BT-B-AB titres in excess of 10 mU/ml on the mouse diaphragm assay. Doubling the last effective BT-B dose produced neither therapeutic effects nor side effects. Subsequent applications of botulinum toxin type A produced a continued therapeutic response in one patient and complete therapy failure in the other.Despite the small sample size a frequency of 44 % indicates a high risk for BT-B-AB-induced complete therapy failure. The high amount of neurotoxin administered when NeuroBloc/MyoBloc is used might be a contributory factor. Further prospective comparative studies are necessary to monitor the frequency and time course of BT-B-AB formation.
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PMID:Botulinum toxin type B de novo therapy of cervical dystonia: frequency of antibody induced therapy failure. 1576 72

With the advent of a commercial preparation of botulinum toxin type B (BT-B) for treatment of cervical dystonia detection of antibodies against BT-B (BT-B-AB) becomes necessary. For this purpose, we carried out a mouse diaphragm assay (MDA) by continuous measurement of the twitch force of a mouse hemidiaphragm preparation elicited by electric stimulation of its phrenic nerve. After exposing the preparation to BT-B 3 ng/ml the time to half-maximal twitch force reduction (paralysis time [PT]) was 69 +/- 4 min (n = 25). Addition of sera from patients with antibodies against BT-A produced a PT of 68 +/- 5 min (n = 24), whereas addition of sera from controls with antibodies against tetanus toxoid produced a PT of 67 +/- 6 min (n = 30). When defined amounts of BT-B-AB were added to the MDA, PT was prolonged. This prolongation was correlated closely to the amount of BT-B-AB added, thus producing a calibration curve. The threshold for BT-B-AB detection was 0.4 mU/ml. When sera from 7 patients (4 women, 3 men; age 50.6 +/- 14.2 years) with cervical dystonia (Toronto Western Spasmodic Torticollis Rating Scale score, 18.9 +/- 2.9) and complete secondary failure of BT-B therapy (NeuroBloc; Elan Pharmaceuticals, Shannon, Ireland; 12,229 +/- 2,601 MU/injection series, 1.86 +/- 0.69 injection series before complete secondary therapy failure; 100.4 +/- 15.8 days between injection series with normal therapeutic effect) were tested, BT-B-AB titers of more than 10 mU/ml were found in all of them. The MDA can be used to measure neutralizing BT-B-AB titers quantitatively and with adequate sensitivity and specificity. Further studies are necessary to understand the role of intermediate BT-B-AB titers in partial BT-B therapy failure.
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PMID:Mouse diaphragm assay for detection of antibodies against botulinum toxin type B. 1607 16