Learning from the past: historical aspects of bacterial toxins as pharmaceuticals

Pellett, Sabine

doi:10.1016/j.mib.2012.05.005

Cited by 20 publications

(14 citation statements)

References 48 publications

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“…The ham had been eaten by victims of a botulism outbreak traced to a funeral in Ellezelles, a village in Belgium. Van Ermengem called the microorganism Bacillus botulinus , 14,18 but it wasn’t until the German physician Ludwig Brieger coined the term “toxin” in 1890 19 that this became associated with Kerner and van Ermengem’s findings.…”

Section: From Sausages To Strabismusmentioning

confidence: 99%

“…18 Initially, microbiologists believed food contaminated with toxin produced by C. botulinum caused all adult cases of botulism. However, in California in 1931, an infant was suspected as having contracted botulism.…”

Section: From Sausages To Strabismusmentioning

confidence: 99%

“…29 In 1946, Carl Lamanna et al at Fort Detrick purified crystalline BoNT-A. 18 This paved the way for therapeutic applications of BoNT, beginning with strabismus.…”

Section: From Sausages To Strabismusmentioning

confidence: 99%

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AbobotulinumtoxinA: A 25-Year History

Monheit

Pickett

2017

Aesthetic Surgery Journal

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During the late 1960s and early 1970s, Alan Scott showed that intramuscular injections of botulinum toxin (BoNT) corrected nonaccommodative strabismus without resorting to surgery. The UK doctors who trained with Scott soon realized the significant potential offered by BoNT type A as a therapeutic option for several difficult-to-treat diseases. This led to a collaboration between these pioneering clinicians and the Centre for Applied Microbiology and Research at Porton Down, United Kingdom, and, in turn, to the development and commercialization of abobotulinumtoxinA as Dysport (Dystonia/Porton Down; Ipsen Biopharm Ltd., Wrexham, UK). Dysport was approved in Europe for the treatment of specific dystonias in December 1990 and now has marketing authorizations in 75 countries. Since then, the use of BoNT in therapeutic and aesthetic indications has grown year-on-year, and continues to expand well beyond Scott’s initial aim. For example, ongoing trials are assessing potential new indications for BoNT-A, including acne and psoriasis. Furthermore, a growing number of other BoNT products, often termed “biosimilars,” together with innovative formulations of well-established BoNT types, are likely to reach the market over the next few years. This review focuses on the history of Dysport to mark the 25th anniversary of its first launch in the United Kingdom.

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Section: From Sausages To Strabismusmentioning

confidence: 99%

Section: From Sausages To Strabismusmentioning

confidence: 99%

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AbobotulinumtoxinA: A 25-Year History

Monheit

Pickett

2017

Aesthetic Surgery Journal

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“…Once inside, the complex is cleaved, freeing LC, which serves as enzyme cleaving SNARES. 294, 295 SNAREs mobilize vesicles for transmitter release and aid in the transport of GLUA1 AMPA receptor subunits to the membrane. 296 In case of SNARE cleavage, transmitter release is blocked.…”

Section: Survey Of Current Targets Of Pain Therapeuticsmentioning

confidence: 99%

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Knezevic

Yekkirala

Yaksh

2017

Anesthesia &Amp; Analgesia

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Opioids Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management, has limitations and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of re-enforcing activity in the absence of a pain state. The present work provides a non-exclusive overview of current drug targets and potential future directions of research and development. We discuss channels activators and blockers, including: sodium channel blockers, potassium channel activators and calcium channel blockers; glutamate receptor targeted agents, including: NMDA, AMPA and metabotropic receptors). Further, we discuss therapeutics targeted at GABA, alpha2 adrenergic and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors, and agonists/antagonists of adenosine, purine receptors. And cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of drugable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising pre-clinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans’ targets, which should assist in developing non-addictive analgesics.

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“…The HC enables the uptake of the complex into the cell. Once in the cell, the complex is cleaved freeing the LC, which is the active enzyme cleaving SNARES [391]. SNAREs play an important role in mobilizing vesicles for transmitter release and in enabling movement of certain proteins to the membrane, such as the GLUA1 AMPA receptor subunits [392].…”

Section: Toxins Coupled To Agonists For G-protein-coupled Receptorsmentioning

confidence: 99%

Current and Future Issues in the development of spinal agents for the management of pain

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.Keywords: Adenovirus transfection, dorsal horn, neurotoxins, pain pathways, spinal drug delivery, spinal analgesics, toxicity. RATIONALETargeting analgesic drugs for direct spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn. Thus, high intensity (e.g., nociceptive) stimulation activates populations of small primary afferents, generating an intensity-dependent increase in activity of second order dorsal horn projection neurons. This excitation is transmitted through spinofugal projection pathways to higher centers, such as the somatosensory thalamus -somatosensory cortex, and to the medial thalamus -limbic cortices that are respectively believed to underlie the sensory-discriminative and affectivemotivational components of the pain experience [1-3]. The dorsal horn encoding process reflects a remarkable plasticity wherein the input-output function of the spinal dorsal horn is subject to pronounced regulation by local neuronal and nonneuronal circuits as well as supraspinal (bulbospinal) input. Thus, following tissue or nerve injury there is an enhanced neuronal response to moderate or low intensity stimuli, e.g., *Address correspondence to this author at the University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, USA; ...

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Learning from the past: historical aspects of bacterial toxins as pharmaceuticals

Cited by 20 publications

References 48 publications

AbobotulinumtoxinA: A 25-Year History

AbobotulinumtoxinA: A 25-Year History

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Current and Future Issues in the development of spinal agents for the management of pain

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