RT Journal Article
SR Electronic
T1 New botulinum neurotoxin constructs for treatment of chronic pain
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201631
DO 10.26508/lsa.202201631
VO 6
IS 6
A1 Charlotte Leese
A1 Claire Christmas
A1 Judit Mészáros
A1 Stephanie Ward
A1 Maria Maiaru
A1 Stephen P Hunt
A1 Bazbek Davletov
YR 2023
UL https://www.life-science-alliance.org/content/6/6/e202201631.abstract
AB 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.