Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum toxin type B (BTX-B) is a member of a family of neurotoxins produced by the anaerobic bacteria Clostridium botulinum. BTXs specifically inhibit acetylcholine release at the neuromuscular junction and cause muscle paralysis in humans. The mechanism of action of BTXs involves inactivation of the neural exocytotic pathway by proteolytic cleavage of components of the exocytotic apparatus. Purified BTXs have been used clinically to treat disorders of muscle contraction, such as spasticity and dystonia. BTXs are purified as high molecular weight complexes that contain additional bacterial proteins which function to protect the toxin molecule. BTX complexes are stable in solution only at acidic pH. A new method was developed to purify intact BTX-B complexes. The resulting liquid formulation of high specific activity BTX-B (Elan's BTX-B evaluated as NeuroBloc) is buffered at pH 5.6 and demonstrates long-term stability at 2 to 25 degrees C.
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PMID:The biochemistry of botulinum toxin type B. 1118 81

The botulinum neurotoxins (BTX) are an exciting group of therapeutic agents with dramatically expanding clinical indications. The US FDA has approved BOTOX (BTX-A, Allergan) and Myobloc (BTX-B, Elan Pharmaceuticals) for the treatment of cervical dystonia. TPP Canada has also approved BOTOX for the treatment of glabellar frown lines. The US FDA is expected to approve this new indication before the end of 2002. These changes will dramatically expand the marketing of BTXs. Concerns about risks and side-effects diminish as clinical experience increases with this "most poisonous of poisons". In particular, the incidence of secondary resistance to the toxin's effect has been dramatically diminished with the reduction of the non-toxic protein in current batches of BOTOX.
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PMID:Update on the botulinum neurotoxins. 1181 96

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