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At least 19 recordsLinked to original sources

PubMed2006

Novel cutaneous uses for botulinum toxin type A.

Botulinum toxin type A is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It has been used extensively in the field of dermatology for the treatment of dynamic rhytides and in the treatment of hyperhidrosis. Botulinum toxin has an excellent safety profile and few side effects when used for these purposes. Recently, botulinum toxin has also been used experimentally in a number of other dermatologic conditions with good results. These conditions include: persistent facial flushing, gustatory sweating and epiphora, anal fissures, familial benign pemphigus (Hailey-Hailey disease), dyshidrotic eczema, and following surgical wound closures. While randomized, controlled prospective trials are still needed to further understand the efficacy and safety of botulinum toxin in these conditions, anecdotal and case report data suggest that botulinum toxin is both safe and efficacious in these and many other procedures.

Administration, Cutaneous↗

PubMed2006

Neurophysiological effects of botulinum toxin type A.

Botulinum toxin type A (BoNT-A) acts peripherally by inhibiting acetylcholine release from the presynaptic neuromuscular terminals, thus weakening muscle contraction, and its clinical benefit depends primarily on the toxin's peripheral action. In addition to acting directly at the neuromuscular junction, the toxin alters sensory inputs to the central nervous system, thus indirectly inducing secondary central changes. Some of the long-term clinical benefits of BoNT-A treatment may also reflect plastic changes in motor output after the reorganization of synaptic density.

Animals↗

PubMed2005

Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A.

Botulinum toxin type A (BOTOX) has been used to treat pathological pain conditions although the mechanism is not entirely understood. Subcutaneous (s.c.) BOTOX also inhibits inflammatory pain in the rat formalin model, and the present study examined whether this could be due to a direct action on sensory neurons. BOTOX (3.5-30 U/kg) was injected s.c. into the subplantar surface of the rat hind paw followed 1-5 days later by 50 mL of 5% formalin. Using microdialysis, we found that BOTOX significantly inhibited formalin-induced glutamate release (peak inhibitions: 35%, 41%, and 45% with 3.5, 7, and 15 U/kg, respectively). BOTOX also dose dependently reduced the number of formalin-induced Fos-like immunoreactive cells in the dorsal horn of the spinal cord and significantly (15 and 30 U/kg) inhibited the excitation of wide dynamic range neurons of the dorsal horn in Phase II but not Phase I of the formalin response. These results indicate that s.c. BOTOX inhibits neurotransmitter release from primary sensory neurons in the rat formalin model. Through this mechanism, BOTOX inhibits peripheral sensitization in these models, which leads to an indirect reduction in central sensitization.

Analgesics↗

PubMed2006

Progress in applying the Three Rs to the potency testing of Botulinum toxin type A.

Botulinum toxin type A (BTA) is being increasingly used for a range of therapeutic purposes and also for cosmetic reasons. For many years, the potency of BTA has been measured by using an LD50 assay in mice. This assay is a cause for concern due to its unpleasant nature and extreme severity, and the requirement for high numbers of mice to be used. Alternatives to this potency assay are presently reviewed with particular reference to the work at the National Institute for Biological Standards and Control (NIBSC), and to recent work by the UK manufacturer of the substance. An in vivo local paralysis assay with considerably less severity has been developed and is in use at the NIBSC. Alternative, ex vivo functional assays in use include the measurement of BTA-induced paralysis of neurally-stimulated rodent diaphragm or rat intercostal muscle. The latter method has the advantage of allowing more preparations to be derived from one animal. However, these ex vivo methods have not yet been fully validated and accepted by regulatory agencies as potency assays. Endopeptidase assays, although not measuring muscle paralysis directly, may provide a very useful consistency test for batch release and may replace the routine use of the LD50 test for that purpose. These assays measure the cleavage of the SNAP-25 protein (the final stage of BTA action), and have been validated for batch release by the National Control Laboratory (NIBSC), and are in regular use there. ELISA assays, used alongside the endopeptidase assay, also provide useful confirmatory information on the amounts of functional (and non-functional) BTA present. The UK manufacturer is further validating its endopeptidase assay, an ex vivo muscle assay and an ELISA. It is anticipated that their work will lead to a change in the product license, hopefully within the next two years, and will form a critical milestone towards the end of the LD50 potency test.

Acetylcholine↗

PubMed2005

Comparison of the therapeutic indexes of different molecular forms of botulinum toxin type A.

Botulinum toxin is produced by Clostridium botulinum in three different molecular-weight forms: LL toxin, 900 kDa; L toxin, 500 kDa; and M toxin, 300 kDa. We isolated the M toxin, then compared its muscle-weakening efficacy with those of L+LL toxin and BOTOX both in vitro and in vivo. The twitch tension of the mouse isolated phrenic nerve-hemidiaphragm was used for the in vitro study. For the in vivo study, grip strength was measured in the toxin-injected legs. Undesirable muscle weakening was evaluated by grip-strength measurement in the contralateral leg. Concentration-response curves for effects on the phrenic nerve-hemidiaphragm showed that M toxin was 10 times more potent than L+LL toxin. The therapeutic index in vivo was 3- to 5-times higher for M toxin than for L+LL toxin or BOTOX, indicating a greater separation for M toxin between doses with local efficacy and systemic toxicity. These findings indicate that the M toxin preparation may have a better pharmacological profile than the conventional preparation.

Animals↗

PubMed2006

Clinical use of non-A botulinum toxins: botulinum toxin type C and botulinum toxin type F.

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia, but some patients are primarily or become secondarily resistant to it. Consequently, other serotypes have to be used when immuno-resistance is proven. In the literature, patients with focal dystonia have been treated with BoNT serotype F with clinical benefit but with short lasting effects. Recently, BoNT serotype C has been used with positive clinical outcome. An update on the clinical use of BoNT serotype F and BoNT serotype C is provided.

Adult↗

PubMed2005

Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. It is characterized by involuntary posturing of the head and frequently is associated with neck pain. Disability and social withdrawal are common. Most cases are idiopathic, and generally it is a life-long disorder. In recent years, botulinum toxin type A (BtA) has become first line therapy for cervical dystonia. However, not all patients respond well to BtA, and 5 to 10% become resistant to it. Botulinum toxin B (BtB) is an alternative to BtA and offers the potential to help patients who do not respond to BtA. At present there is no compelling theoretical reason why it should not be as effective as, or even more effective than, BtA. OBJECTIVES: To compare the clinical efficacy and safety of BtA versus BtB in cervical dystonia. SEARCH STRATEGY: Studies for inclusion in the review were identified using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, by handsearching the Movement Disorders Journal and abstracts of international congresses on movement disorders and botulinum toxin, by communication with other researchers in the field, by searching reference lists of papers found using the above search strategies, and by contact with authors and drug manufacturer. SELECTION CRITERIA: Studies were considered eligible for inclusion in the review if they evaluated the efficacy of BtA versus BtB for the treatment of cervical dystonia. Trials must have been randomised and placebo-controlled. DATA COLLECTION AND ANALYSIS: A paper pro-forma was used to collect data from the included studies using double extraction by two independent reviewers. Each trial was assessed for internal validity by each of the two reviewers. Differences were settled by discussion. The outcome measures used included improvement in symptomatic rating scales, subjective evaluation by patients and clinicians, changes in pain scores, changes in quality of life assessments, and frequency and severity of adverse events. MAIN RESULTS: We cannot give any results since we have only identified two ongoing trials and there are no preliminary results or interim analyses available for them. The full results of these trials are expected in late 2004 or 2005. AUTHORS' CONCLUSIONS: It is currently not possible to make definitive comparisons between BtA and BtB for the treatment of cervical dystonia; uncontrolled comparisons should be regarded with suspicion.

Botulinum Toxins↗

PubMed2003

Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset and radius of diffusion.

BACKGROUND: Botulinum toxin types A and B can improve the appearance of facial wrinkles. Differences in the time until onset and the degree of diffusion have been observed anecdotally, but no direct comparative studies have been done. OBJECTIVE: To compare the rate of onset and the radius of diffusion of botulinum toxin types A and B in the rhytides of the forehead. METHODS: Adults with symmetrical moderate to severe forehead wrinkles at full contracture received botulinum toxin type A (BOTOX; 5 U) on one side of the forehead and type B (MYOBLOC; 500 U) on the other side. Photographs taken at rest and full frontalis contracture were analyzed by computer, and a time-lapse motion picture was created. Radius of diffusion and time until full effect were measured. RESULTS: Botulinum toxin type B had a slightly faster onset of action than type A. All patients responded to type B quickly, whereas some had a delayed response to type A. A greater radius of diffusion was consistently observed with botulinum toxin type B, as measured by the greater area of wrinkle reduction at the doses used. CONCLUSIONS: In this comparative study of patients with symmetrical forehead wrinkles, botulinum toxin type B produced a greater area of diffusion and a more rapid onset of action than type A.

Adult↗

PubMedDate not supplied

Comparison between intramuscular and perimuscular injections of botulinum toxin type A.

BACKGROUND: Botulinum toxin type A (BTX-A) must be injected in the intramuscular area to exert its paralytic effect. The durability of the BTX-A effect varies in different patients, and this fact can result from different locations of the drug injection, for example, the muscle peripheral area (perimuscular). This study aimed to evaluate whether a difference exists in the effect duration of the muscle paralysis between intramuscular and perimuscular injections of BTX-A. METHODS: This study used 18 male New Zealand rabbits divided into two groups (A and B) based on the location of the BTX-A injection. The group A animals received 10 units of BTX-A diluted with 0.1 ml of normal saline injected perimuscularly. The group B animals received the same dosage injected in the intramuscular area of the left masseter muscle. An electroneurophysiologic study was performed 1 week before the experiment for all the animals, then repeated 1, 4, and 8 weeks after the toxin injection. RESULTS: The amplitude values recorded in the masseter muscle were significantly lower in both groups throughout the study than the physiologic amplitude. The comparison between groups A and B did not show any statistically significant amplitude variations throughout the 8 weeks. CONCLUSION: No significant difference in the neuromuscular blockade induced by botulinum toxin type A was observed between injections into the muscle peripheral area and intramuscular injections.

Animals↗

PubMedDate not supplied

Inhibition of exocytosis in bovine adrenal medullary cells by botulinum toxin type D.

Botulinum toxins are known to block transmitter release at peripheral cholinergic synapses, producing muscular weakness and paralysis. The toxins may also block adrenergic transmission, although this effect is less well understood. The mechanisms by which toxins act are unclear. They are proteins of relative molecular mass approximately 150,000 and are structurally similar to tetanus toxin. It is generally accepted that a rise in intracellular calcium concentration is sufficient to trigger secretion by exocytosis, but it is not known whether the toxins block secretion by preventing this Ca transient or whether they act downstream from Ca entry by interfering with the process of exocytosis itself. We have attempted to resolve these questions in the case of the adrenergic system by studying the effects of botulinum toxins (types A, B, D and E) on the secretory response of isolated bovine adrenal medullary cells maintained in culture. The cells were either challenged with various secretagogues or rendered leaky and challenged directly with Ca buffers. We report here that botulinum toxin type D inhibits secretion in a time- and dose-dependent manner, the results being entirely consistent with the idea that the toxin acts at or near the site of exocytosis rather than at the sites controlling the rise in free Ca.

Acetylcholine↗

PubMed2003

Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A.

BACKGROUND: Botulinum toxin type B (BTX-B; Myobloc) has recently been introduced for the treatment of dynamic rhytides. This serotype is structurally similar to botulinum toxin type A (BTX-A; Botox) and appears to produce equivalent muscular paralysis. Because of the fact that some patients may become resistant to the effects of BTX-A with its continued use or may require large doses of type A to exert adequate muscular paralysis, the use of BTX-B may prove beneficial in these cases. OBJECTIVE: To determine the effect of BTX-B on glabellar rhytides refractory or showing decreased clinical effect to treatment with BTX-A. METHODS: Twenty females (mean age, 43 years) with vertical glabellar rhytides showing decreased or negligible clinical effect to BTX-A were treated with intramuscular injections of BTX-B. Five standardized intramuscular sites (procerus, inferomedial corrugator muscles, superior middle corrugator muscles) received a total dose of 2,500 U. Patients were evaluated at pretreatment and 48 to 72 hours, 1 week, and 2 and 4 months after injection. RESULTS: All glabellar rhytides improved after treatment with BTX-B injections. Peak clinical effect was noted 1 month after treatment, with 50% of peak effect evident at the 2-month follow-up. Near complete dissolution of effect was seen at 4 months after treatment. Side effects were transient and were limited to moderate injectional pain and rare bruising and frontal brow tightness. CONCLUSIONS: BTX-B is an effective treatment modality for glabellar rhytides refractory or exhibiting decreased clinical effect to BTX-A. The duration of effect using the 2,500 U dosing schedule described herein was shorter than that typically achieved after equivalent BTX-A injection.

Adult↗

PubMed1998

Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A.

OBJECTIVE: A previous study of botulinum toxin type F (BTX-F) treatment for torticollis had shown a dose of 520 MU to be effective, but for a much shorter duration than is usual with botulinum toxin type A (BTX-A). The objective was to assess the effect of a higher dose of BTX-F. METHODS: Four of the previously treated patients, plus an additional patient, were treated with a higher dose of 780 MU BTX-F. All were secondary nonresponders to BTX-A due to neutralising antibodies. A test injection of 40 MU BTX-F was also given into the extensor digitorum brevis muscle (EDB), to examine the time course of the biological effect of the toxin electrophysiologically. Patients were followed up at two, four, eight, and 12 weeks. RESULTS: All patients reported subjective improvement lasting from seven to 11 (mean 8.6) weeks accompanied by a significant reduction in mean clinical severity scores at two weeks. Four patients had pain which was substantially reduced. The electrophysiological studies confirmed biological sensitivity to the toxin in all patients, showing a significant change beginning at two weeks and returning to baseline at 12 weeks. The time course of this effect paralleled roughly that of the clinical response. The four patients who had previously received 520 MU BTX-F reported that the response was better and longer in duration with 780 MU. Dysphagia was more common than reported with the lower dose. CONCLUSION: Better results are possible with higher doses of BTX-F but the duration of benefit is still shorter than with BTX-A, seemingly due to a shorter duration of neuromuscular junction blockade.

Adult↗

PubMed2000

The biochemistry of botulinum toxin type B.

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.

Botulinum Toxins↗

PubMed2003

Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure.

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.

Adult↗

PubMed2001

Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions.

Botulinum toxin type A is an important therapeutic agent for the treatment of movement and other disorders. As the clinical uses of botulinum toxin type A expand, it is increasingly important to understand the biochemical and pharmacological actions of this toxin, as well as those of other botulinum toxin serotypes (B-G). Botulinum neurotoxin serotypes exhibit differences in neurotoxin complex protein size, percentage of neurotoxin in the activated or nicked form, intracellular protein target, and potency. These properties differ even between preparations that contain the same botulinum toxin serotype due to variations in product formulations. As demonstrated in preclinical and clinical studies, these differences result in a unique combination of efficacy, duration of action, safety, and antigenic potential for each botulinum neurotoxin preparation.

Animals↗

PubMed2003

[First use of botulinum toxin type B in ENT patients with secondary therapy failure of botulinum toxin type A].

The first botulinum toxin type B (BT-B) formulation, NeuroBloc, has been licensed in Germany for the treatment of cervical dystonia since March 2001. This allows the treatment of patients with secondary failure of botulinum type A (BT-A) injections for the first time. Three patients with such a secondary failure were successfully treated with BT-B. A total of 1,000 mouse units (MU) NeuroBloc per eye were injected in a patient with blepharospasm. The treatment was effective for 4 months. In a patient with spasmodic dysphonia, 250 MU were injected into each vocal cord. This was effective for 3.5 months. The third patient suffered from bilateral Frey's syndrome. A total of 7,500 MU were used on the right side and 6,000 MU on the left side to stop the gustatory sweating for 9 months. Overall, BT-B showed similar intervals of effectiveness as BT-A. Side effects were not seen using the above dosage regimes.

Aged↗

PubMed2003

[Botulinum toxin type B in the management of dystonia non-responsive to botulinum toxin type A].

BACKGROUND: Botulinum toxin (BTX) injection is the first choice treatment for focal dystonias. However 10% or more of patients who receive repetitive injections of BTX type A (BTX-A) lose response (secondary non-responders). One of the strategies to manage such patients is to treat them with another serotype. The aim of this article is to describe my experience with BTX type B (BTX-B) in the management of patients with focal dystonia who became secondary non-responders to BTX-A. METHOD: Open-label non-controlled use of BTX-B injections to treat dystonia patients who developed secondary nonresponse to BTX-A Response to treatment was rated on a 0-4 scale (Jankovic). RESULTS: Four patients entered the study. Pacient 1- At age 48 this man developed idiopathic cervical dystonia. Five years later he also presented with blepharospasm and idiopathic oromandibular dystonia. He was treated with 7604U of BTX-A along 23 sessions separated by a mean interval of 18.8 weeks (range 6-39). Loss of response was noticed after the seventh session. First treatment with BTX-B consisted of injection of 20000U with response rated 3 but duration of 3 weeks. Second session, 23500U, resulted in score 4 with response lasting 12 weeks. Patient 2- This man, with Tourette syndrome since age 8 years, developed tardive blepharospasm at age 51. On 8 sessions of BTX-A injections he received a cumulative dosage of 550U with a mean interval between sessions of 8.8 weeks (range 6-12). Decline of response was noticed after the fifth session. First treatment with BTX-B, 3000U, had a response rated 3 with duration of 12 weeks. Second session, 6000U, resulted in score 4. Patient 3- This woman noticed onset of blepharospasm at age 58 and developed oromandibular and laryngeal dystonia as well as cervical dystonia, respectively, at ages 59 and 65. In other institutions she received 6 sessions of BTX-A. In my service she received a dosage of 1404U along 8 sessions with a mean interval between sessions of 17.4 weeks (range 16-18). She became secondary non-responder after the ninth session. First treatment with BTX-B, 6000U, was rated 0. Second session, 12000U, was rated 4. Patient 4- At age 69 this man developed idiopathic cranial dystonia. Prior to follow up with me, he received 6 sessions of BTX-A in other services. In my institution he was treated with a cumulative dosage of 730U along 4 sessions with a mean interval between sessions of 16.3 weeks (range 15-18). He developed loss of response on the sixth session. Treatment with BTX-B, 12000U, was rated 4 and lasted 20 weeks. Side-effects: local pain (all patients) and dryness of mouth and ptosis (one patient each). CONCLUSION: My findings confirm that BTX-B injections are a safe and effective option for the management of dystonia patients who become secondary non-responders to BTX-A. The results also underscore the need of individualizing dosage regimens before optimum results are achieved.

Aged↗

PubMed2002

[Initial experiences with clinical use of botulinum toxin type B].

Recently, botulinum toxin type B (BT-B) was introduced for treatment of cervical dystonia (CD). We wish to report on experience with BT-B derived from registration studies and from our own preliminary clinical experience. Botulinum toxin type B can be used successfully in CD patients with antibody-induced failure of botulinum toxin type A therapy (antibody patients). In our own 15 antibody patients, 11835 +/- 2,039 mouse units of BT-B (NeuroBloc) reduced the Toronto Western spasmodic torticollis rating scale (TWSTRS) score from 20.5 +/- 3.6 to 13.1 +/- 5.4. BT-B can also be used successfully in CD patients not previously exposed to BT-A or BT-B (de novo patients). In our own nine de novo patients, 10436 +/- 3,320 mouse units of BT-B reduced the TWSTRS score from 18.4 +/- 5.4 to 9.2 +/- 4.8. Altogether, dryness of the mouth occurred in 21 CD patients (severe 10, moderate 7, mild 4), accommodation difficulties in seven, conjunctival irritation in five, reduced sweating in four, swallowing difficulties in three, heartburn in three, constipation in three, bladder voiding difficulties in two, and dryness of nasal mucosa, head instability, and thrush in one each. BT-B produces substantially more systemic autonomic side effects than BT-A. It can be considered the therapy of choice in antibody patients. For de novo patients and for BT-A-treated CD patients, BT-B cannot be recommended currently.

Adult↗