Purpose: A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT.
Methods: We determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model.
Results: drBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin.
Conclusions: Based on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11095-015-1816-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BoNT/Action beyond neurons.
Toxicon
January 2025
National Research Council of Italy, Institute of Biochemistry and Cell Biology, 00015, Monterotondo, RM, Italy. Electronic address:
Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control.
View Article and Find Full Text PDFPreventive Effects of Botulinum Neurotoxin Long-Term Therapy: Comparison of the 'Experienced' Benefits and 'Suspected' Worsening Across Disease Entities.
J Clin Med
January 2025
Department of Neurology, University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Repetitive intramuscular injections of botulinum neurotoxin (BoNT) have become the treatment of choice for a variety of disease entities. But with the onset of BoNT therapy, the natural course of a disease is obscured. Nevertheless, the present study tries to analyze patients' "suspected" course of disease severity under the assumption that no BoNT therapy had been performed and compares that with the "experienced" improvement during BoNT treatment.
View Article and Find Full Text PDFBotulinum Toxin: A Comprehensive Review of Its Molecular Architecture and Mechanistic Action.
Int J Mol Sci
January 2025
Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA 02747, USA.
Botulinum toxin (BoNT), the most potent substance known to humans, likely evolved not to kill but to serve other biological purposes. While its use in cosmetic applications is well known, its medical utility has become increasingly significant due to the intricacies of its structure and function. The toxin's structural complexity enables it to target specific cellular processes with remarkable precision, making it an invaluable tool in both basic and applied biomedical research.
View Article and Find Full Text PDFINCUOLATION THE BOTULINUM TOXIN-B IN THE ZYGOMITICUS OF THE RAT, FOLLOWED BY EVALUATION IT'S EFFECT HISTOLOGICALLY ON THE ZYGOMATIC BONE.
Georgian Med News
November 2024
1Department of biology, College of Education for Women, University of Kirkuk, Iraq.
Background: Botulinum toxin is an attenuated neurotoxin of Clostridium Botulinum gram positive bacterial, which is used in medication sialorrhea, cervical dystonia, hyperhidrosis and non-surgical cosmetic operation (aesthetic) such as facial wrinkles and reduced the bulky appearance hypertrophied of masseter muscle. This study was designed to revealed the effect of zygomiticus inoculation of botulinum toxin B in zygomatic muscle of rats on zygomatic bone.
Methods: A total of 25 male albino rats (200-260 gm) were injected facial intramuscular by a single dose of 2.
Delphi Consensus on the Management of Spanish Patients with Post-Stroke Hemiplegic Shoulder Pain Treated with Botulinum Toxin A: Result Study.
Toxins (Basel)
January 2025
Doctor Negrín University Hospital of Gran Canaria, Pl. Barranco de la Ballena s/n, 35010 Las Palmas de Gran Canaria, Spain.
The study aimed to identify expert opinions and obtain recommendations on the management of post-stroke hemiplegic shoulder pain (HSP) and treatment with botulinum toxin A (BoNT-A). A multicenter Delphi study was conducted using an online survey designed by a committee of experts with at least 10 years of experience in post-stroke HSP management with BoNT-A in Spain. Forty-seven panelists (specialists with at least 5 years of experience in post-stroke HSP management with BoNT-A) rated their level of agreement in two rounds based on acceptance by ≥66.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!