A Novel Botulinum Neurotoxin Topical Gel: Treatment of Allergic Rhinitis in Rats and Comparative Safety Profile

Zhu, Zhao; Stone, Hongran F.; Thach, Thai Q.D.; Garcia, L. Rodriguez; Ruegg, Curtis L.

doi:10.2500/ajra.2012.26.3785

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…One other area where needle-free delivery of BoNT/A has been explored is topical intranasal delivery. Successful intranasal delivery of BoNT/A and the relief of symptoms of allergic rhinitis in rats was achieved using the proprietary CPP RT001 formulation [ 185 ]. Effective relief of idiopathic rhinitis in some patients has been reported following simple intranasal application of a sponge soaked in BoNT/A solution [ 186 ].…”

Section: Novel Delivery Methodsmentioning

confidence: 99%

The Expanding Therapeutic Utility of Botulinum Neurotoxins

Fonfría

Maignel

Lezmi

et al. 2018

Toxins

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Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products.

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Section: Novel Delivery Methodsmentioning

confidence: 99%

The Expanding Therapeutic Utility of Botulinum Neurotoxins

Fonfría

Maignel

Lezmi

et al. 2018

Toxins

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“…Based on published data, several types of non‐neuronal cells may be directly affected by BoNT in human skin and other tissues that produce a biological effect. The cells expressing one or more of the BoNT/A‐binding proteins SV2, FGFR3 or vanilloid receptors, and/or BoNT/A cleavage target SNAP‐25, include epidermal keratinocytes, mesenchymal stem cells from subcutaneous adipose, nasal mucosal cells, urothelial cells, intestinal epithelial cells, prostate epithelial cells, alveolar epithelial cells, T47D, MDA‐MB‐231 and MDA‐MB‐453 breast cell lines, neutrophils and macrophages . Importantly, it has been reported that, in addition to SNAP‐25, BoNT/A can also cleave SNAP‐23, which is ubiquitously expressed in human tissues .…”

Section: The Structure and Function Of Botulinum Neurotoxinsmentioning

confidence: 99%

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond

Grando

Zachary

2018

Br J Dermatol

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There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the non-neuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNTs. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. non-neuronal cells. The non-neuronal cells that express one or more BoNT/A-binding proteins, and/or cleavage target synaptosomal-associated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT/A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an anti-ageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anticancer properties. BoNTs have a much wider range of applications than originally understood, and the individual cellular responses to the cholinergic impacts of BoNTs could provide fertile ground for future studies.

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“…Every day intranasal administration of ovalbumin is necessary to maintain allergic signs. Sneezing, nasal itching (nasal rubbing), rhinorrhea and congestion are useful signs to indications of allergic rhinitis (62,63).…”

Section: Ovalbumin-induced Allergic Rhinitis Modelmentioning

confidence: 99%

Animal model of allergy and asthma; protocol for researches

Athari¹,

Nasab²,

Athari³

2019

Preprint

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Allergic diseases and asthma are an important problem in health system and effects large amounts of people in the worlds. Exposure to outdoor and indoor allergens promote the sensitization towards these allergens. Th2 cytokines are main stimulators allergic diseases initiation. Allergic diseases similar to other diseases have been studied in animal for understanding of pathophysiology and treatments. Animal models provide a potential approach to investigation of the pathophysiology, mechanism and drugs designing for allergy and asthma. Physicians and veterinarians with collaboration in this field could improve best animal model. In this review, it will be discussed the various models (especially in mouse) and protocols by focusing on the allergic diseases. Animal models in allergy field, are applicable for important goals. Moral discussion in all procedures should be remarkable.

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A Novel Botulinum Neurotoxin Topical Gel: Treatment of Allergic Rhinitis in Rats and Comparative Safety Profile

Abstract: These results suggest that topical intranasal application of RT001 is effective in relief of clinical signs and inflammatory pathology associated with allergic rhinitis in a rodent model and may provide a safe treatment for rhinitis.

Cited by 14 publications

References 34 publications

The Expanding Therapeutic Utility of Botulinum Neurotoxins

The Expanding Therapeutic Utility of Botulinum Neurotoxins

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond

Animal model of allergy and asthma; protocol for researches

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