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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/28614091/injectable-daxibotulinumtoxina-for-the-treatment-of-glabellar-lines-a-phase-2-randomized-dose-ranging-double-blind-multicenter-comparison-with-onabotulinumtoxina-and-placebo
#1
Jean Carruthers, Nowell Solish, Shannon Humphrey, Nathan Rosen, Channy Muhn, Vince Bertucci, Arthur Swift, Andrei Metelitsa, Roman G Rubio, Jacob Waugh, John Quiring, Gill Shears, Alastair Carruthers
BACKGROUND: Injectable daxibotulinumtoxinA (RT002) is an investigational botulinum toxin Type A in clinical development. It is formulated with a proprietary peptide and offers the potential of a longer acting neurotoxin therapy. OBJECTIVE: To compare the safety, efficacy, and duration of response of daxibotulinumtoxinA with onabotulinumtoxinA and placebo [www.clinicaltrials.gov NCT02303002]. METHODS: In this Phase 2, randomized, dose-ranging, parallel-group, double-blind, multicenter study, subjects with moderate or severe glabellar lines at maximum frown were randomly assigned to 20U, 40U, or 60U daxibotulinumtoxinA, 20U onabotulinumtoxinA, or placebo...
June 12, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28596838/botulinum-neurotoxins-serotypes-a-and-b-induce-paralysis-of-mouse-striated-and-smooth-muscles-with-different-potencies
#2
Jacquie Maignel-Ludop, Marion Huchet, Johannes Krupp
To address the scarcity of direct comparison of botulinum neurotoxin serotypes activity on smooth versus striatal muscle, we have studied the action of BoNT/A1 and BoNT/B1 on ex vivo preparations of both muscle types. We have set up and characterized a model of neurogenic contractions in the isolated mouse bladder, and used this model to explore the effects of the two serotypes on contractions evoked by electrical field stimulation. Both toxins were also tested in the mouse phrenic nerve hemidiaphragm assay, to compare their potency in smooth versus striated muscle...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28587791/evaluation-of-anti-botulinum-neurotoxin-single-domain-antibodies-with-additional-optimization-for-improved-production-and-stability
#3
Lisa C Shriver-Lake, Dan Zabetakis, Ellen R Goldman, George P Anderson
Botulinum neurotoxin (BoNT) is a highly potent and lethal toxin, which even in minute quantities can lead to death. BoNT occurs in seven well described serotypes, A-G, and it is critical to not only detect the presence of BoNT, but also to determine the serotype to which a person has been exposed, as the degree of toxicity and persistence of symptoms varies greatly between the various types. Recently, Conway et al. 2010 developed single domain antibodies (sdAb), the recombinant variable domains of heavy-chain-only antibodies derived from camelids, for the detection of all seven serotypes of BoNT; identifying pairs of sdAb for each serotype they demonstrated the sensitive detection of each toxin...
June 3, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28584101/deubiquitinating-enzyme-vcip135-dictates-the-duration-of-botulinum-neurotoxin-type-a-intoxication
#4
Yien Che Tsai, Archana Kotiya, Erkan Kiris, Mei Yang, Sina Bavari, Lino Tessarollo, George A Oyler, Allan M Weissman
Botulism is characterized by flaccid paralysis, which can be caused by intoxication with any of the seven known serotypes of botulinum neurotoxin (BoNT), all of which disrupt synaptic transmission by endoproteolytic cleavage of SNARE proteins. BoNT serotype A (BoNT/A) has the most prolonged or persistent effects, which can last several months, and exerts its effects by specifically cleaving and inactivating SNAP25. A major factor contributing to the persistence of intoxication is the long half-life of the catalytic light chain, which remains enzymatically active months after entry into cells...
June 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28566161/long-term-safety-of-repeated-high-doses-of-incobotulinumtoxina-injections-for-the-treatment-of-upper-and-lower-limb-spasticity-after-stroke
#5
Andrea Santamato, Francesco Panza, Domenico Intiso, Alessio Baricich, Alessandro Picelli, Nicola Smania, Francesca Fortunato, Davide Seripa, Pietro Fiore, Maurizio Ranieri
Current guidelines suggested a dosage up to 600units (U) of botulinum toxin type A (BoNT-A) (onabotulinumtoxinA or incobotulinumtoxinA) in reducing spastic hypertonia with low prevalence of complications, although a growing body of evidence showed efficacy with the use of high doses (>800U). The available evidence mainly referred to a single set of injections evaluating the efficacy and safety of the neurotoxin 30days after the treatment. In a prospective, non-randomized, open-label study, we studied the safety of repeated higher doses of incobotulinumtoxinA in post-stroke upper and lower limb spasticity...
July 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28556093/recovery-of-rat-muscle-size-but-not-function-more-than-1-year-after-a-single-botulinum-toxin-injection
#6
Samuel R Ward, Viviane B Minamoto, Kentaro P Suzuki, Jonah B Hulst, Shannon N Bremner, Richard L Lieber
INTRODUCTION: Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin-injected adult rat skeletal muscle over nearly the entire lifespan. METHODS: Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT-A); Allergan, Irvine, California] or saline solution injection. Neurotoxin-injected animals (n = 90) were analyzed at different time-points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months...
May 26, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28546483/finished-whole-genome-sequences-of-two-clostridium-botulinum-type-a-b-isolates
#7
Jessica L Halpin, Karen Hill, Shannon L Johnson, David Carlton Bruce, T Brian Shirey, Janet K Dykes, Carolina Lúquez
Clostridium botulinum secretes a potent neurotoxin that causes devastating effects when ingested, including paralysis and death if not treated. In the United States, some clinically significant strains produce toxin type A while also harboring a silent B gene. These are the first two closed genome sequences published for this subset.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28546482/finished-whole-genome-sequence-of-clostridium-argentinense-producing-botulinum-neurotoxin-type-g
#8
Jessica L Halpin, Karen Hill, Shannon L Johnson, David Carlton Bruce, T Brian Shirey, Janet K Dykes, Carolina Lúquez
Here, we present a closed genome sequence for Clostridium argentinense strain 89G, the first strain identified to produce botulinum neurotoxin type G (BoNT/G). Although discovered in 1970, to date, there have been no reference quality sequences publicly available for this species.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28537692/long-term-response-of-different-botulinum-toxins-in-refractory-neurogenic-detrusor-overactivity-due-to-spinal-cord-injury
#9
Giuseppe Lombardi, Stefania Musco, Giovanni Bacci, Maria Celso, Valerio Bellio, Giulio Del Popolo
PURPOSE: To assess the response in spinal cord injured patients alternatively treated with different types and dosages of Botulinum neurotoxin type A (BoNT/A) over 15 years. MATERIAL AND METHODS: Patients who underwent first BoNT/A from 1999-2001 and practiced intermittent catheterization were included. Baseline 3-day bladder diary (BD) and urodynamics were collected. BoNT/A failure was defined when patients asked for re-injection ≤ 3 months post-treatment. Criteria for re-injection was at least one daily episode of urinary incontinence at BD...
May 23, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28522711/draft-genome-sequences-of-five-brazilian-clostridium-botulinum-group-iii-type-d-c-strains
#10
Cédric Woudstra, Roseane B Brito, Antônio A Fonseca Júnior, Rodrigo O S Silva, Francisco C F Lobato, Patrick Fach
Animal botulism is mainly associated with Clostridium botulinum group III-producing neurotoxin types C, C/D, D, and D/C. In this report, we present the draft genome sequences of the first five strains of Clostridium botulinum type D/C isolated in Brazil and used for vaccination purposes.
May 18, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28522038/injectable-and-topical-neurotoxins-in-dermatology-basic-science-anatomy-and-therapeutic-agents
#11
REVIEW
Cerrene N Giordano, Seth L Matarasso, David M Ozog
Botulinum toxin is a potentially deadly anaerobic bacterial toxin that acts by inhibiting release of acetylcholine at the neuromuscular junction, thereby inhibiting contraction of the exposed striated muscle. There are currently 4 botulinum toxin preparations approved by the US Food and Drug Administration (FDA): onabotulinumtoxin, abobotulinumtoxin, incobotulinumtoxin and rimabotulinumtoxin. While significant overlap exists, each product has unique properties and specifications, including dosing, diffusion, and storage...
June 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28491822/comparison-of-the-expression-changes-after-botulinum-toxin-type-a-and-minocycline-administration-in-lipopolysaccharide-stimulated-rat-microglial-and-astroglial-cultures
#12
Anna Piotrowska, Katarzyna Popiolek-Barczyk, Flaminia Pavone, Joanna Mika
Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28458568/cost-effectiveness-analysis-of-abobotulinumtoxina-for-the-treatment-of-cervical-dystonia-in-the-united-kingdom
#13
Madhusubramanian Muthukumar, Kamal Desai, Seye Abogunrin, Timothy Harrower, Sylvie Gabriel, Jerome Dinet
BACKGROUND: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness. OBJECTIVE: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective. METHODS: A Markov model was developed to evaluate the cost-effectiveness of abobotulinum-toxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male)...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28455330/regulation-of-botulinum-neurotoxin-synthesis-and-toxin-complex-formation-by-arginine-and-glucose-in-clostridium-botulinum-atcc-3502
#14
Chase M Fredrick, Guangyun Lin, Eric A Johnson
Botulinum neurotoxin (BoNT) produced by neurotoxigenic clostridia is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation are not well studied. Previous studies indicated that growth and BoNT formation was affected by arginine and glucose in C. botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine, glucose and three products of arginine metabolism, citrulline, proline and ornithine...
April 28, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28450105/optimization-of-snap-25-derived-peptide-substrate-for-improved-detection-of-botulinum-a-in-the-endopep-ms-assay
#15
Osnat Rosen, Liron Feldberg, Eyal Dor, Sigalit Gura, Ran Zichel
Botulinum neurotoxins (BoNTs) are the most toxic proteins in nature. Endopeptidase-mass-spectrometry (Endopep-MS) is used as a specific and rapid in-vitro assay to detect BoNTs. In this assay, immunocaptured toxin cleaves a serotype-specific-peptide-substrate, and the cleavage products are then detected by MS. Here we describe the design of a new peptide substrate for improved detection of BoNT type A (BoNT/A). Our strategy was based on reported BoNT/A-SNAP-25 interactions integrated with analysis method efficiency considerations...
July 1, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28445195/protective-effect-of-botulinum-toxin-type-a-against-atopic-dermatitis-like-skin-lesions-in-nc-nga-mice
#16
Sang Bum Han, Hyeree Kim, Sang Hyun Cho, Jin Ho Chung, Hei Sung Kim
BACKGROUND: Botulinum neurotoxin (BTX) A possesses various biological activities, including anti-inflammatory and antipruritic actions. Human and animal studies have shown that BTX is effective in treating histamine-induced itch, lichen simplex chronicus, psoriasis, rosacea, allergic rhinitis, and scar prevention. However, its effect on atopic dermatitis (AD) has not been studied yet. OBJECTIVE: To examine the effect of BTX on AD using a mouse model. The primary outcome was skin thickness and transepidermal water loss (TEWL), and the secondary outcome was the alteration in skin severity scores, histological, and laboratory test results...
April 24, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#17
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427139/-advances-in-the-research-of-mechanism-in-prevention-and-treatment-of-scar-with-botulinum-toxin-type-a-and-its-clinical-application
#18
Y H Li, J Q Liu, D Xiao, W Zhang, D H Hu
Scar is a common complication in wound healing process, and how to effectively prevent and treat it is a hot and difficult problem in burns and plastic surgery field. Botulinum toxin type A is a neurotoxin that has been widely and effectively used in the cosmetic surgery field such as anti-wrinkle and thin face. In recent years, botulinum toxin type A has been applied in prevention and treatment of scar, which causes a great concern. Nowadays, the relevant reports have gradually increased, and the mechanisms have been explored more deeply...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28410268/long-term-anti-itch-effect-of-botulinum-neurotoxin-a-is-associated-with-downregulation-of-trpv1-and-trpa1-in-the-dorsal-root-ganglia-in-mice
#19
Lei-Fang Cao, Meng Si, Ya Huang, Li-Hua Chen, Xiao-Yan Peng, Ya-Qin Qin, Teng-Teng Liu, Yan Zhou, Tong Liu, Wei-Feng Luo
Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice...
April 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28389376/botulinum-neurotoxin-type-a-cleaved-snap25-is-confined-to-primary-motor-neurons-and-localized-on-the-plasma-membrane-following-intramuscular-toxin-injection
#20
Brian B Cai, Joseph Francis, Mitchell F Brin, Ron S Broide
The mechanism of action of botulinum neurotoxin type A (BoNT/A) is well characterized, but some published evidence suggests the potential for neuronal retrograde transport and cell-to-cell transfer (transcytosis) under certain experimental conditions. The present study evaluated the potential for these processes using a highly selective antibody for the BoNT/A-cleaved substrate (SNAP25197) combined with 3-dimensional imaging. SNAP25197 was characterized in a rat motor neuron (MN) pathway following toxin intramuscular injections at various doses to determine whether SNAP25197 is confined to MNs or also found in neighboring cells or nerve fibers within spinal cord (SC)...
June 3, 2017: Neuroscience
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