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Toxins Jan 2021Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal... (Review)
Review
Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal dystonia, despite short-term clinical benefits and the risks of adverse effects. To cater for the high demand across various medical specialties, at least six US Food and Drug Administration (FDA)-approved formulations of BoNT are currently available for diverse labelled indications. The toxo-pharmacological properties of these formulations are not uniform and thus should not be used interchangeably. Synthetic BoNTs and BoNTs from non-clostridial sources are not far from clinical use. Moreover, the study of mutations in naturally occurring toxins has led to modulation in the toxo-pharmacokinetic properties of BoNTs, including the duration and potency. We present an overview of the toxo-pharmacology of conventional and novel BoNT preparations, including those awaiting imminent translation from the laboratory to the clinic.
Topics: Bacterial Toxins; Botulinum Toxins; Drug Compounding; Drug Development; Drug Prescriptions; Humans; Nervous System Diseases; Neuromuscular Agents; Neuromuscular Junction; Recombinant Proteins
PubMed: 33466571
DOI: 10.3390/toxins13010058 -
American Family Physician Aug 2014Botulinum toxin injection for treatment of facial wrinkles is the most frequently performed cosmetic procedure in the United States, and it is one of the most common... (Review)
Review
Botulinum toxin injection for treatment of facial wrinkles is the most frequently performed cosmetic procedure in the United States, and it is one of the most common entry procedures for clinicians seeking to incorporate aesthetic treatments into their practice. Treatment of frown lines and crow's feet, which are the cosmetic indications approved by the U.S. Food and Drug Administration, and horizontal forehead lines, offers predictable results, has few adverse effects, and is associated with high patient satisfaction. Wrinkles are formed by dermal atrophy and repetitive contraction of underlying facial musculature. Botulinum toxin is a potent neurotoxin that inhibits release of acetylcholine at the neuromuscular junction. Injection of small quantities of botulinum toxin into specific overactive muscles causes localized muscle relaxation that smooths the overlying skin and reduces wrinkles. Botulinum toxin effects take about two weeks to fully develop and last three to four months. Dynamic wrinkles, seen during muscle contraction, yield more dramatic results than static wrinkles, which are visible at rest. Botulinum toxin injection is contraindicated in persons with keloidal scarring, neuromuscular disorders (e.g., myasthenia gravis), allergies to constituents of botulinum toxin products, and body dysmorphic disorder. Minor bruising can occur with botulinum toxin injection. Temporary blepharoptosis and eyebrow ptosis are rare complications that are technique-dependent; incidence declines as injector skill improves.
Topics: Botulinum Toxins, Type A; Cosmetic Techniques; Face; Humans; Injections, Intradermal; Neuromuscular Agents; Skin Aging
PubMed: 25077722
DOI: No ID Found -
Journal of Neural Transmission (Vienna,... Jun 2022Although botulinum toxin (BT) is now being used in a large number of different indications in numerous medical specialties, there is still dynamic and rapid development.... (Review)
Review
Although botulinum toxin (BT) is now being used in a large number of different indications in numerous medical specialties, there is still dynamic and rapid development. Treatment algorithms were improved by the introduction of BT short-interval therapy, BT high-dose therapy and improved dosing guidelines. Ultrasound guidance may be helpful in special situations. New indication areas including depression and inflammatory processes are being explored. Drug development projects are mainly focusing on onabotulinumtoxinA analogues, some are addressing liquid preparations and modifications of BT's duration of action. Recombinant BT may simplify production processes. Cell-based assays for potency measurement will soon be required by registration authorities. Treatment algorithms will be further refined and indications will be expanded. New indication areas are still uncertain. BT type A will remain the drug substance of choice. Removal of complexing proteins seems logical. Whether there is a need for BT drugs with modified duration of action and for liquid preparations, is unclear. Bringing BT therapy to those who need it, is the biggest challenge. Current high-price business models need to be changed, either by employing a biosimilar registration approach or by referring to companies from countries where business models are based on different cost structures.
Topics: Algorithms; Botulinum Toxins, Type A
PubMed: 35396965
DOI: 10.1007/s00702-022-02494-5 -
Journal of Neural Transmission (Vienna,... Apr 2021Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for... (Review)
Review
Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for BT therapy. When BT is injected into dystonic muscles, it produces a peripheral paresis which is localised, well controllable and follows a distinct and predictable time course of around 3 months. Adverse effects are always transient and usually mild, long-term application is safe. With this profile BT can be used to treat cranial dystonia, cervical dystonia and limb dystonia including writer's and musician's cramps. The recent introduction of BT high dose therapy also allows to treat more wide-spread dystonia including segmental and generalised dystonia. BT can easily be combined with other anti-dystonic treatments such as deep brain stimulation and intrathecal baclofen application. Best treatment results are obtained when BT therapy is integrated in the multimodal and long-term 'multilayer concept of treatment of dystonia'. The biggest challenge for the future will be to deliver state of the art BT therapy to all dystonia patients in need, regardless of whether they live in developed countries or beyond.
Topics: Botulinum Toxins; Botulinum Toxins, Type A; Dystonic Disorders; Humans; Muscles; Torticollis; Treatment Outcome
PubMed: 33125571
DOI: 10.1007/s00702-020-02266-z -
Toxins Aug 2019Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B),... (Review)
Review
Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are currently in clinical use. While considered safe and effective, their use has been rarely complicated by the development of antibodies that reduce or negate their therapeutic effect. The presence of antibodies has been attributed to shorter dosing intervals (and booster injections), higher doses per injection cycle, and higher amounts of antigenic protein. Other factors contributing to the immunogenicity of BoNT include properties of each serotype, such as formulation, manufacturing, and storage of the toxin. Some newer formulations with purified core neurotoxin devoid of accessory proteins may have lower overall immunogenicity. Several assays are available for the detection of antibodies, including both structural assays such as ELISA and mouse-based bioassays, but there is no consistent correlation between these antibodies and clinical response. Prevention and treatment of antibody-associated non-responsiveness is challenging and primarily involves the use of less immunogenic formulations of BoNT, waiting for the spontaneous disappearance of the neutralizing antibody, and switching to an immunologically alternate type of BoNT.
Topics: Animals; Antibodies, Neutralizing; Binding Sites, Antibody; Botulinum Toxins, Type A; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Serogroup
PubMed: 31454941
DOI: 10.3390/toxins11090491 -
Toxins Feb 2020Botulinum neurotoxin (BoNT) is a potent biological toxin and powerful therapeutic tool for a growing number of clinical orofacial applications. BoNT relaxes striated... (Review)
Review
INTRODUCTION
Botulinum neurotoxin (BoNT) is a potent biological toxin and powerful therapeutic tool for a growing number of clinical orofacial applications. BoNT relaxes striated muscle by inhibiting acetylcholine's release from presynaptic nerve terminals, blocking the neuromuscular junction. It also has an antinociceptive effect on sensory nerve endings, where BoNT and acetylcholine are transported axonally to the central nervous system. In dentistry, controlled clinical trials have demonstrated BoNT's efficiency in pathologies such as bruxism, facial paralysis, temporomandibular joint (TMJ) disorders, neuropathic pain, sialorrhea, dystonia and more.
AIM
This study's aim was to conduct a systematic literature review to assess the most recent high-level clinical evidence for BoNT's efficacy and for various protocols (the toxin used, dilution, dosage and infiltration sites) used in several orofacial pathologies.
MATERIALS AND METHODS
We systematically searched the MedLine database for research papers published from 2014 to 2019 with randomly allocated studies on humans. The search included the following pathologies: bruxism, dislocation of the TMJ, orofacial dystonia, myofascial pain, salivary gland disease, orofacial spasm, facial paralysis, sialorrhea, Frey syndrome and trigeminal neuralgia.
RESULTS
We found 228 articles, of which only 20 met the inclusion criteria: bruxism (four articles), orofacial dystonia (two articles), myofascial pain (one article), salivary gland disease (one article), orofacial spasm (two articles), facial paralysis (three articles), sialorrhea (four articles) or trigeminal neuralgia (three articles).
DISCUSSION
The clinical trials assessed showed variations in the dosage, application sites and musculature treated. Thus, applying BoNT can reduce symptoms related to motor muscular activity in the studied pathologies efficiently enough to satisfy patients. We did not identify the onset of any important side effects in the literature reviewed. We conclude that treatment with BoNT seems a safe and effective treatment for the reviewed pathologies.
Topics: Botulinum Toxins; Clinical Trials as Topic; Facial Pain; Humans; Myofascial Pain Syndromes; Neuromuscular Agents; Temporomandibular Joint Disorders; Treatment Outcome
PubMed: 32053883
DOI: 10.3390/toxins12020112 -
Toxins Jan 2021Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved... (Review)
Review
Since its initial approval in 1989 by the US Food and Drug Administration for the treatment of blepharospasm and other facial spasms, botulinum toxin (BoNT) has evolved into a therapeutic modality for a variety of neurological and non-neurological disorders. With respect to neurologic movement disorders, BoNT has been reported to be effective for the treatment of dystonia, bruxism, tremors, tics, myoclonus, restless legs syndrome, tardive dyskinesia, and a variety of symptoms associated with Parkinson's disease. More recently, research with BoNT has expanded beyond its use as a powerful muscle relaxant and a peripherally active drug to its potential central nervous system applications in the treatment of neurodegenerative disorders. Although BoNT is the most potent biologic toxin, when it is administered by knowledgeable and experienced clinicians, it is one of the safest therapeutic agents in clinical use. The primary aim of this article is to provide an update on recent advances in BoNT research with a focus on novel applications in the treatment of movement disorders. This comprehensive review of the literature provides a critical review of evidence-based clinical trials and highlights recent innovative pilot studies.
Topics: Botulinum Toxins; Dyskinesias; Humans; Movement Disorders; Neurotoxins; Restless Legs Syndrome
PubMed: 33430071
DOI: 10.3390/toxins13010042 -
Toxins Aug 2017Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used... (Review)
Review
Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves inhibiting the release of inflammatory mediators and peripheral neurotransmitters from sensory nerves. Recent journals have demonstrated that BoNT is effective for neuropathic pain, such as postherpetic neuralgia, trigeminal neuralgia, and peripheral neuralgia. The purpose of this review is to summarize the experimental and clinical evidence of the mechanism by which BoNT acts on various types of neuropathic pain and describe why BoNT can be applied as treatment. The PubMed database was searched from 1988 to May 2017. Recent studies have demonstrated that BoNT injections are effective treatments for post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, and intractable neuropathic pain, such as poststroke pain and spinal cord injury.
Topics: Animals; Botulinum Toxins; Humans; Neuralgia; Protein Conformation
PubMed: 28837075
DOI: 10.3390/toxins9090260 -
Arquivos de Neuro-psiquiatria Mar 2005This review describes therapeutically relevant mechanisms of action of botulinum toxin (BT). BT's molecular mode of action includes extracellular binding to... (Review)
Review
This review describes therapeutically relevant mechanisms of action of botulinum toxin (BT). BT's molecular mode of action includes extracellular binding to glycoproteine structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain-barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated through blockade of substance P, glutamate and calcitonin gene related peptide.
Topics: Anti-Dyskinesia Agents; Autonomic Nervous System; Botulinum Toxins; Central Nervous System; Dose-Response Relationship, Drug; Humans; Muscle, Skeletal; Neuromuscular Junction; Reflex, Stretch
PubMed: 15830090
DOI: 10.1590/s0004-282x2005000100035 -
Advances in Therapy Oct 2021Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There... (Review)
Review
Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There are seven serotypes of BoNT (serotypes A-G); BoNT-A and BoNT-B are the botulinum toxin serotypes utilized for therapeutic applications. Treatment with BoNT injections is used to manage chronic medical conditions across multiple indications. As with other biologic drugs, immunogenicity after long-term treatment with BoNT formulations may occur, and repeated use can elicit antibody formation leading to clinical nonresponsiveness. Thus, approaching BoNT treatment of chronic conditions with therapeutic formulations that minimize stimulating the host immune response while balancing patient responsiveness to therapy is ideal. Immunogenicity is a clinical limitation in many settings that use biologic drugs for treatment, and clinically relevant immunogenicity reduction has been achieved through engineering smaller protein constructs and reducing unnecessary formulation components. A similar approach has influenced the evolution of BoNT formulations. Three BoNT-A products and one BoNT-B product have been approved by the Food and Drug Administration (FDA) for therapeutic use: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB; a fourth BoNT-A product, daxibotulinumtoxinA, is currently under regulatory review. Additionally, prabotulinumtoxinA is a BoNT-A product that has been approved for aesthetic indications but not therapeutic use. Here, we discuss the preclinical and clinical immunogenicity data that exist within the scientific literature and provide a perspective for considering immunogenicity as a key factor in choice of BoNT formulation.
Topics: Botulinum Toxins; Humans; United States
PubMed: 34515975
DOI: 10.1007/s12325-021-01882-9