Unlabeled uses of botulinum toxins: A review, part 1

Cheng, Christine; Chen, Jennifer; Patel, Rosalie P.

doi:10.2146/ajhp050137

Cited by 57 publications

(41 citation statements)

References 34 publications

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Section: Snap23 ͉ Snap25 ͉ Snare Proteinsmentioning

confidence: 99%

“…The clinical use of BoNTs is limited to targeting inflictions affecting neuromuscular activity (11,12). Elucidation of the structure-function relationship of BoNTs has enabled the design of therapies that retarget BoNT to unique neurons and nonneuronal cells.…”

Section: Snap23 ͉ Snap25 ͉ Snare Proteinsmentioning

confidence: 99%

“…As early as 1989, BoNT/A was approved by the FDA to treat strabismus, blepharospam, and hemificial spasm and then for cervical dystonia, cosmetic use, glabellar facial lines, and axillary hyperhidrosis (11). BoNT/A efficacy in dystonia and other disorders related to involuntary skeletal muscle activity, coupled with a satisfactory safety profile, has prompted empirical/off-label use in a variety of secretions and pain and cosmetic disorders (12).The clinical use of BoNTs is limited to targeting inflictions affecting neuromuscular activity (11,12). Elucidation of the structure-function relationship of BoNTs has enabled the design of therapies that retarget BoNT to unique neurons and nonneuronal cells.…”

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confidence: 99%

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Engineering botulinum neurotoxin to extend therapeutic intervention

Chen

Barbieri

2009

Proc. Natl. Acad. Sci. U.S.A.

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Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K 224 D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K 224 D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.Clostridium botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans (1). BoNTs elicit neuronal-specific flaccid paralysis by targeting neurons and cleaving neuronspecific soluble N-ethylmaleimide-sensitive fusion proteinattachment protein receptors (SNARE) proteins. BoNTs are organized into 3 functional domains: an N-terminal zinc-metalloprotease light chain (LC), a translocation domain (HCT), and a C-terminal receptor binding domain (HCR) (1, 2). BoNTs bind luminal domains of synaptic vesicle proteins, upon the fusion of synaptic vesicles with the plasma membrane (3-5). BoNTs are internalized into endosomes and upon acidification, the LC is translocated into the cytoplasm, where SNARE proteins are cleaved (1, 2).Mammalian neuronal exocytosis is driven by the formation of protein complexes between the vesicle SNARE, VAMP2, and the plasma membrane SNAREs, SNAP25 and syntaxin 1a (6). There are 7 serotypes of BoNTs (termed A-G) that cleave specific residues on 1 of 3 SNARE proteins: serotypes B, D, F, and G cleave VAMP-2, serotypes A and E cleave SNAP25, and serotype C cleaves SNAP25 and syntaxin 1a (1). Thus, neuronal specificity is based upon BoNT binding to neurons and cleaving neuronal isoforms of the SNARE proteins. For example, BoNT/A cleaves human SNAP25, but not the human nonneuronal isoform SNAP23 (7,8). The nonneuronal SNARE isoforms are involved in divergent cellular processes, including fusion reactions in cell growth, membrane repair, cytokinesis, and synaptic transmission (reviewed in 9).The reversible nature of muscle function after BoNT intoxication that replace toxin-affected nerves with new nerves (10) has turned the BoNT from a deadly agent to therapies for neu...

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Section: Snap23 ͉ Snap25 ͉ Snare Proteinsmentioning

confidence: 99%

Section: Snap23 ͉ Snap25 ͉ Snare Proteinsmentioning

confidence: 99%

mentioning

confidence: 99%

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Engineering botulinum neurotoxin to extend therapeutic intervention

Chen

Barbieri

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…3 Treatment of AMPS requires a multidisciplinary approach, with the goals of interrupting the pain cycle, abolishing the myofascial trigger points, and restoring muscle flexibility by eliminating predisposing factors and perpetuation of the pain. 18 In addition to symptomatic treatment with analgesics, muscle relaxants, antidepressants, and nonsteroidal anti-inflammatory drugs (NSAIDs), 13 specific treatments, such as local anesthetic blockade in trigger points, [19][20][21][22] ischemic compression, 13,23,24 electrotherapy, 25 and Botulinum toxin [26][27][28][29][30] may be tried. Alternative or complementary therapies have also been used increasingly for musculoskeletal pain.…”

Section: Introduction Cmentioning

confidence: 99%

Effect of Acupuncture on Chronic Pelvic Pain Secondary to Abdominal Myofascial Syndrome Not Responsive to Local Anesthetic Block: A Pilot Study

Mitidieri

Gurian

Silva

et al. 2017

Medical Acupuncture

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Objective: Strong evidence shows that 85% of women with chronic pelvic pain (CPP) have musculoskeletal disorders, such as abdominal myofascial pain syndrome (AMPS). The aim of this research was to assess the efficacy of local acupuncture treatment for women with CPP secondary to AMPS unresponsive to treatment with trigger-point injection. Materials and Methods: This pilot study involved 17 women with moderate-to-severe AMPS-related CPP. Acupuncture treatments were given at abdominal-wall trigger points once per week for 10 consecutive weeks. Pain relief was assessed with a visual analogue scale (VAS), the McGill questionnaire, and pressure dynamometer. Quality of life and psychosocial function (risk for anxiety and depression) were evaluated using the Short-Form-36 questionnaire and the Hospital Anxiety and Depression scale. Assessments were performed at baseline and after 1, 3, and 6 months of treatment. Results: Both the VAS and McGill pain questionnaire showed significantly decreased pain intensity (VAS, P < 0.001; and McGill, P 0.049), and the effects were sustained even at 6 months after treatment. Conclusions: Acupuncture treatment was effective for the women who participated in this study, and the current authors believe that these preliminary results suffice to recommend performing randomized controlled trials.

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“…Its effect starts three to four days after application and remains four to six months, when, it is believed, regeneration or proliferation of new nerve terminals occurs and promote and re-establish the motor endplate (1,2) . Over 2.5 million esthetic procedures using BTX-A were performed in 2008 in the USA.…”

Section: Introductionmentioning

confidence: 99%

Botox® after Botox® - a new approach to treat diplopia secondary to cosmetic botulinic toxin use: case reports

Isaac¹,

Chalita²,

Pinto³

2012

Arq. Bras. Oftalmol.

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A new technique for the treatment of diplopia secondary to cosmetic botulinum to xin A use is described. In this interventional case reports, two consecutive patients who developed diplopia after periocular cosmetic use of botulinum toxin A were treated with intramuscular botulinum toxin A injection into the antagonist ex traocular muscle. Diplopia resolved in both patients in less than 1 week with no side effects or complications. In conclusion, the injection of intramuscular botulinum toxin A is an encouraging option for treatment of diplopia secondary to botulinum toxin A use for facial lifting.

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Unlabeled uses of botulinum toxins: A review, part 1

Cited by 57 publications

References 34 publications

Engineering botulinum neurotoxin to extend therapeutic intervention

Engineering botulinum neurotoxin to extend therapeutic intervention

Effect of Acupuncture on Chronic Pelvic Pain Secondary to Abdominal Myofascial Syndrome Not Responsive to Local Anesthetic Block: A Pilot Study

Botox® after Botox® - a new approach to treat diplopia secondary to cosmetic botulinic toxin use: case reports

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