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

Botulism, which was first reported over a century ago, is caused by botulinum neurotoxins produced by Clostridium botulinum in seven immunological serotypes (A through G). The primary structures of a number of these BoNTs have been determined and are reviewed here, together with their gene structure and synthesis. The biological actions of BoNTs, which result in their ability to block neurotransmitter release have been the subject of intensive study, and in this review we discuss the binding of BoNTs to the cell surface as well as the mechanism of their intercellular action. The ability of BoNTs to block neurotransmitter release has been exploited in therapeutic applications to reduce muscle hyperactivity for the treatment of a variety of clinical conditions associated with involuntary muscle spasm and contractions. The advantages, limitations, and risks of these applications are discussed. Certain compounds provide some limited protection against BoNT. However, more effective protection has been obtained immunologically either by passive immunity (i.e., by administration of anti-BoNT Abs) or by immunization with inactivated toxin. More recently, excellent protection has been obtained by immunization with the receptor-binding region comprising the C-terminal (residues 860 to 1296) fragment (Hc) of the heavy chain of BoNT/A. Here we review the mapping of the epitopes on the Hc region of BoNT/A that are recognized by anti-BoNT/A Abs raised in horse, human, and mouse. The epitopes on the Hc that are recognized by anti-Hc Abs and by Hc-primed T lymphocytes were mapped in two mouse strains [BALB/c (H-2d) and SJL (H-2s)]. The peptides, which contain Ab or T cell epitopes (or both) on the Hc, were used as immunogens in BALB/c and SJL mice and we identified those peptides whose Ab and/or T-cell response cross-react with Hc. Identification of these peptides is an important first step in the intricate requirements for the design of a synthetic vaccine.
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PMID:Structure, activity, and immune (T and B cell) recognition of botulinum neurotoxins. 1042

Intramuscular injection of botulinum neurotoxin A is a relatively new method for treating spastic movement disorders in children. One major goal of any therapy for patients with movement disorders is to improve gross motor function. In this study, 18 patients with adductor spasm were treated with botulinum neurotoxin A. Treatment effect was determined with the Gross Motor Function Measure, a standardized, validated instrument designed to assist in assessment of gross motor function. Spastic muscle hyperactivity and joint mobility were evaluated by the modified Ashworth Scale and by range of motion, respectively. Compared to pretreatment values, significant improvement in gross motor function (P < .010), decrease in the modified Ashworth Scale, and increase in the range of motion (P < .010) were achieved. Patients with moderate impairment of gross motor function (classed at level III and level IV in the Gross Motor Function Classification System) benefited most from treatment. In patients with severe handicap (level V), only one of five treated patients showed improvement in gross motor function. Nevertheless, all patients in this subgroup benefited from improved ease in hygienic care. In conclusion, we have demonstrated that for most children with moderate functional impairment, the Gross Motor Function Measure is a useful instrument for objective documentation of improvements of gross motor function following treatment with botulinum neurotoxin A.
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PMID:Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure. 1080 85

Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.
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PMID:Botulinum toxin (BoNT) and back pain. 1499 38

This single-site, open-label, dose-finding study evaluated the safety and efficacy of botulinum toxin type B (BoNT-B; Myobloc) for the treatment of adductor spasmodic dysphonia (AdSD) in 13 patients. Three patients received a total of 50 U (25 U per vocal fold); the same three subsequently received 100 U, and then 10 more received 200 U. The primary measure of efficacy was the patient's rating of the change in the severity of spasms on a scale from -3 to +3. There were seven secondary measures of efficacy, including blinded ratings of the sound of voice recorded on audiotape. At Week 8 after injection, spasms improved in 0 of 3 patients who received 50 U, 1 of 3 patients who received 100 U, and 8 of 10 patients who received 200 U. The mean (+/- standard deviation [SD]) score for the change in spasm severity at Week 8 in the 200 U group was 1.4 (+/-1.2) points (P = 0.004). All seven secondary measures also showed improvement. Breathiness was the most common side effect but was mild in intensity and of short duration. We conclude that BoNT-B is safe and effective for the treatment of adductor spasmodic dysphonia.
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PMID:Safety and efficacy of botulinum toxin type B (Myobloc) in adductor spasmodic dysphonia. 1537

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

A recent study has demonstrated for the first time that botulinum neurotoxin (BoNT) briefly opens tumour vessels, allowing more effective destruction of cancer cells by radiotherapy and chemotherapy. This review discusses the implications of BoNTs in cancer treatment. After briefly reviewing the different BoNT serotypes, their pharmacological activities and their general use in medicine, the authors focus on their possible application in cancer and describe how BoNTs have been used so far to treat spasm related to tumour or to therapies. By dissecting the mechanisms of action leading to a potentiation of anticancer therapy, it can be seen that BoNTs act by an effect on the tumour microenvironment rather than by a direct cytotoxic effect on tumour cells.
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PMID:Use of botulinum toxins in cancer therapy. 1724 40

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.
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PMID:Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. 1869 73


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