Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intramuscular injections of botulinum neurotoxin type A cause reversible chemodenervation and subsequent paralysis by blocking the presynaptic release of acetylcholine. Botulinum toxin type A has emerged as the most effective form of symptomatic treatment for abnormabilities in muscle movement (blepharospasm, hemifacial spasm, torticollis) and has been approved for use in these conditions. First results in the treatment of patients suffering from oromandibular dystonia, myogenic craniomandibular dysfunction and recurrent dislocation of the temporomandibular joint are presented. In most cases, therapeutic effects occurred within 1-6 days post-injection. Muscular hyperfunction was reliably reduced and involuntary activity patterns gradually ceased. No severe side effects of the local injections were noted.
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PMID:[New techniques in maxillofacial surgery: local injection treatment with botulinum toxin A]. 965 37

Clostridium botulinum, a Gram-positive, anaerobic spore-forming bacteria, is distinguished by its significant clinical applications as well as its potential to be used as bioterror agent. Growing cells secrete botulinum neurotoxin (BoNT), the most poisonous of all known poisons. While BoNT is the causative agent of deadly neuroparalytic botulism, it also serves as a remarkably effective treatment for involuntary muscle disorders such as blepharospasm, strabismus, hemifacial spasm, certain types of spasticity in children, and other ailments. BoNT is also used in cosmetology for the treatment of glabellar lines, and is well-known as the active component of the anti-aging medications Botox and Dysport. In addition, recent reports show that botulinum neurotoxin can be used as a tool for pharmaceutical drug delivery. However, BoNT remains the deadliest of all toxins, and is viewed by biodefense researchers as a possible agent of bioterrorism (BT). Among seven serotypes, C. botulinum type A is responsible for the highest mortality rate in botulism, and thus has the greatest potential to act as biological weapon. Genome sequencing of C. botulinum type A Hall strain (ATCC 3502) is now complete, and has shown the genome size to be 3.89 Mb with a G+C content of approximately 28.2%. The bacterium harbors a 16.3 kb plasmid with a 26.8% G+C content--slightly lower than that of the chromosome. Most of the virulence factors in C. botulinum are chromosomally encoded; bioinformatic analysis of the genome sequence has shown that the plasmid does not harbor toxin genes or genes for related virulence factors. Interestingly, the plasmid does harbor genes essential to replication, including dnaE, which encodes the alpha subunit of DNA polymerase III which has close similarity with its counterpart in C. perfringens strain 13. The plasmid also contains similar genes to those that encode the ABC-type multidrug transport ATPase, and permease. The presence of ABC-type multidrug transport ATPase, and permease suggests putative involvement of efflux pumps in bacteriocin production, modification, and export in C. botulinum. The C. botulinum plasmid additionally harbors genes for LambdaBa04 prophage and site-specific recombinase that are similar to those found in the Ames strain of Bacillus anthracis; these genes and their products may play a role in genomic rearrangement. Completion of genome sequencing for C. botulinum will provide an opportunity to design genomic and proteomic-based systems for detecting different serotypes of C. botulinum strains in the environment. The completed sequence may also facilitate identification of potential virulence factors and drug targets, as well as help characterize neurotoxin-complexing proteins, their polycistronic expression, and phylogenetic relationships between different serotypes.
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PMID:Clostridium botulinum: a bug with beauty and weapon. 1583 1

Since its development for the use of blepharospasm and strabismus more than 2.5 decades ago, botulinum neurotoxin (BoNT) has become a versatile drug in various fields of medicine. It is the standard of care in different disorders such as cervical dystonia, hemifacial spasm, focal spasticity, hyperhidrosis, ophthalmological and otolaryngeal disorders. It has also found widespread use in cosmetic applications. Many other indications are currently under investigation, including gastroenterologic and urologic indications, analgesic management and migraine. This paper is an extensive review of the spectrum of BoNT clinical applications.
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PMID:Botulinum toxin: clinical use. 1687 Apr 87

Botulinum toxin type-A (BoNT-A) prevents the release of acetylcholine at cholinergic junctions, thereby causing temporary muscle weakness lasting 3-4 months. It is now widely used to treat a broad range of clinical disorders characterized by muscle hyperactivity. BoNT-A has proved effective in the management of several neurological conditions and, in particular, in the management of movement disorders (e.g. blepharospasm, cervical dystonia, laryngeal dystonia, limb dystonia, hemifacial spasm, focal tics, tremor and other hyperkinetic disorders). As a treatment of spasticity, BoNT-A can improve mobility and dexterity as well as preventing the development of distressing and costly secondary complications. In cerebral palsy, BoNT-A is of value, being able to delay or even avoid surgery until motion patterns have become established.
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PMID:Clinical value of botulinum toxin in neurological indications. 1711 46

This review updates understanding and research on blepharospasm, a subtype of focal dystonia. Topics covered include clinical aspects, pathology, pathophysiology, animal models, dry eye, photophobia, epidemiology, genetics, and treatment. Blepharospasm should be differentiated from apraxia of eyelid opening. New insights into pathology and pathophysiology are derived from different types of imaging, including magnetic resonance studies. Physiologic studies indicate increased plasticity and trigeminal sensitization. While botulinum neurotoxin injections are the mainstay of therapy, other therapies are on the horizon.
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PMID:Update on blepharospasm: report from the BEBRF International Workshop. 1885 43

Spasticity is characterized by increased muscle resistance. It is usually associated with muscle weakness or poor motor control. This condition not only reduces activities of daily living (ADLs), but also interferes personal hygiere and causes caregiuer's difficulty. The use of botulinum neurotoxin (BoNT) intramuscular injections is a simple and effective therapy for spasticity. The use of BoNT to treat adult patients with spasticity was first reported in 1989, since then, using the neurotoxin to treat spasticity became popular in some European countries. Now in Japan, BoNT can be used to treat only torticollis, blepharospasm and hemifacial spasm because of the legal limitation on its use. However, clinical research on the use of BoNT in spasticity caused by stroke is presently underway, and an adaptation of the toxin may be available in the near future. This article reviews the characteristics of BoNT and the techniques for injecting this neurotoxin.
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PMID:[Use of botulinum neurotoxin for spasticity]. 1911 Jul 53

In earlier studies, we have demonstrated the efficacy of albumin-supplemented botulinum toxin type A (ASBTA) in principle. Here, we present long-term data from 106 patients who received ASTBA over 5-10 years for the treatment of cervical dystonia, blepharospasm and hemifacial spasm. Vials of Dysport were diluted in 0.1% albumin solution to a concentration of 25 units/ml. Overall patients and indications, the mean latency to response was 7.1 +/- 2.2 days, the mean duration of response was 12.3 +/- 3.1 weeks and the mean global clinical improvement (scale 0-3) was 2.6 +/- 0.2. Only one patient had neutralizing antibodies against BoNT-A. Side effects were less frequent than known for conventional BoNT-A and generally mild. These findings were confirmed by analysis of data of 71 patients who have been reconverted from ASBTA to conventional dilutions of Dysport or Botox. We conclude that long-term treatment with ASBTA is effective, safe and help to reduce costs.
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PMID:Experience with long-term treatment with albumin-supplemented botulinum toxin type A. 1931 77

Since the late 1970s, local injections of BoNT have provided clinical benefit for patients with inappropriately contracting muscles with or without pain or sensory disturbance. Marketing authorization for some BoNTs, depending on country, include core indications of dystonia (blepharospasm and cervical dystonia), large muscle spastic disorders (not yet approved in the United States, e.g., adult post-stroke spasticity and equinus foot deformity), hyperhidrosis and aesthetic. Subsequent development has extended to selected conditions characterized by recurrent or chronic pain (migraine headache), and urologic indications (neurogenic/idiopathic overactive bladder; prostate hyperplasia), with multiple additional opportunities available. Portfolio management requires a careful individual opportunity assessment of scientific and technical aspects (basic science foundation, potential to treat unmet medical need, product-specific risk in specific populations, therapeutic margin/safety profile, and probability of successful registration pathway). This article describes ongoing development targets for BOTOX.
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PMID:Development of future indications for BOTOX. 1947 Mar 42

Botulism is a severe neuroparalytic disease caused by toxins produced by several Clostridium species. Botulinum toxin has been of concern to the US military and its allies as a biowarfare weapon since World War II and, in more recent times, by the Centers for Disease Control and Prevention (CDC) as a potential bioterrorist threat to the public. The most effective means of defending against the toxin is by inducing a protective immune response through vaccination. Vaccination with an appropriate antigen will produce neutralizing antibodies that will bind to and clear toxin from the circulation before it can enter nerve cells and block neurotransmission. Immunity from botulism, however, has the disadvantage of precluding an individual from realizing the potential benefits of therapeutic botulinum toxin, if such a need were to arise. Botulinum toxin has been used in the treatment of numerous neuromuscular, autonomic, and sensory disorders since it was first approved for the management of strabismus and blepharospasm by the Food and Drug Administration (FDA) in 1989. Notwithstanding the value of the neurotoxin as a therapeutic drug, vaccines have been and will continue to be an important line of defense for those who work with the toxin (at-risk workers) and a select population of the military, law enforcement, and first responders. The first vaccine used to protect against botulinum neurotoxin was a chemically detoxified extract from Clostridium botulinum. A Pentavalent botulinum toxoid (PBT) vaccine in service today is administered under an Investigational New Drug (IND) application held by the CDC. Recombinant subunit vaccines are in development and a bivalent H(c) vaccine (rBV A/B (Pichia pastoris)) is presently being evaluated in a phase II clinical trial. This review focuses on botulism and the development of vaccines for its prevention.
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PMID:Botulism and vaccines for its prevention. 1983 83

Blepharospasm is a focal dystonia in which the extraocular muscles contract repetitively, leading to excessive blinking and forced eyelid closure. Botulinum toxin type A (BoNTA) is the primary symptomatic treatment for blepharospasm and its effects have been evaluated using numerous rating scales. The main scales in use today were initially used to determine whether BoNTA treatment was superior to placebo, and most controlled trials have confirmed this. More recently, these scales have been used to determine whether there are efficacy differences between different BoNTs in blepharospasm. However, although the scales used in these trials are able to differentiate the effects of BoNT from placebo, they may not be sensitive enough to differentiate between BoNTs. Most of the scales include only four possible points for each item, which would necessitate a 25% greater improvement in one group than the other to detect any differences. Current scales are also relatively insensitive to patients with mild disability who may experience mainly psychosocial problems related to their blepharospasm. Clinical trials comparing BoNTs that include substantial numbers of mildly affected patients may be unlikely to find differences because the scales do not adequately measure mild symptoms. Additional challenges with evaluating blepharospasm include the lack of precision and objectivity of current measures, symptom variability, the need to evaluate aspects of the disorder that are most important to patients, and the different types of blepharospasm. Although no single scale may be able to capture all relevant aspects of blepharospasm, more sensitive and patient-centered scales are needed.
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PMID:Difficulties with differentiating botulinum toxin treatment effects in essential blepharospasm. 2122 69


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