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New botulinum neurotoxin constructs for treatment of chronic pain
Chronic pain affects one in five people across human societies, with few therapeutic options available. Botulinum neurotoxin (BoNT) can provide long-lasting pain relief by inhibiting local release of neuropeptides and neurotransmitters, but its highly paralytic nature has limited its analgesic poten...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098373/ https://www.ncbi.nlm.nih.gov/pubmed/37041008 http://dx.doi.org/10.26508/lsa.202201631 |
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author | Leese, Charlotte Christmas, Claire Mészáros, Judit Ward, Stephanie Maiaru, Maria Hunt, Stephen P Davletov, Bazbek |
author_facet | Leese, Charlotte Christmas, Claire Mészáros, Judit Ward, Stephanie Maiaru, Maria Hunt, Stephen P Davletov, Bazbek |
author_sort | Leese, Charlotte |
collection | PubMed |
description | Chronic pain affects one in five people across human societies, with few therapeutic options available. Botulinum neurotoxin (BoNT) can provide long-lasting pain relief by inhibiting local release of neuropeptides and neurotransmitters, but its highly paralytic nature has limited its analgesic potential. Recent advances in protein engineering have raised the possibility of synthesising non-paralysing botulinum molecules for translation to pain sufferers. However, the synthesis of these molecules, via several synthetic steps, has been challenging. Here, we describe a simple platform for safe production of botulinum molecules for treating nerve injury–induced pain. We produced two versions of isopeptide-bonded BoNT from separate botulinum parts using an isopeptide bonding system. Although both molecules cleaved their natural substrate, SNAP25, in sensory neurons, the structurally elongated iBoNT did not cause motor deficit in rats. We show that the non-paralytic elongated iBoNT targets specific cutaneous nerve fibres and provides sustained pain relief in a rat nerve injury model. Our results demonstrate that novel botulinum molecules can be produced in a simple and safe manner and be useful for treating neuropathic pain. |
format | Online Article Text |
id | pubmed-10098373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-100983732023-04-14 New botulinum neurotoxin constructs for treatment of chronic pain Leese, Charlotte Christmas, Claire Mészáros, Judit Ward, Stephanie Maiaru, Maria Hunt, Stephen P Davletov, Bazbek Life Sci Alliance Research Articles Chronic pain affects one in five people across human societies, with few therapeutic options available. Botulinum neurotoxin (BoNT) can provide long-lasting pain relief by inhibiting local release of neuropeptides and neurotransmitters, but its highly paralytic nature has limited its analgesic potential. Recent advances in protein engineering have raised the possibility of synthesising non-paralysing botulinum molecules for translation to pain sufferers. However, the synthesis of these molecules, via several synthetic steps, has been challenging. Here, we describe a simple platform for safe production of botulinum molecules for treating nerve injury–induced pain. We produced two versions of isopeptide-bonded BoNT from separate botulinum parts using an isopeptide bonding system. Although both molecules cleaved their natural substrate, SNAP25, in sensory neurons, the structurally elongated iBoNT did not cause motor deficit in rats. We show that the non-paralytic elongated iBoNT targets specific cutaneous nerve fibres and provides sustained pain relief in a rat nerve injury model. Our results demonstrate that novel botulinum molecules can be produced in a simple and safe manner and be useful for treating neuropathic pain. Life Science Alliance LLC 2023-04-11 /pmc/articles/PMC10098373/ /pubmed/37041008 http://dx.doi.org/10.26508/lsa.202201631 Text en © 2023 Leese et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Leese, Charlotte Christmas, Claire Mészáros, Judit Ward, Stephanie Maiaru, Maria Hunt, Stephen P Davletov, Bazbek New botulinum neurotoxin constructs for treatment of chronic pain |
title | New botulinum neurotoxin constructs for treatment of chronic pain |
title_full | New botulinum neurotoxin constructs for treatment of chronic pain |
title_fullStr | New botulinum neurotoxin constructs for treatment of chronic pain |
title_full_unstemmed | New botulinum neurotoxin constructs for treatment of chronic pain |
title_short | New botulinum neurotoxin constructs for treatment of chronic pain |
title_sort | new botulinum neurotoxin constructs for treatment of chronic pain |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098373/ https://www.ncbi.nlm.nih.gov/pubmed/37041008 http://dx.doi.org/10.26508/lsa.202201631 |
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