summary: Freshly released botulinum neurotoxin can relieve symptoms of chronic pain without causing addiction or nerve damage that leads to paralysis.

source: University of Sheffield

A team of scientists from the Universities of Sheffield, Reading, University College London (UCL) and US-based biopharmaceutical company Neuresta have created a new elongated botulinum neurotoxin that can relieve chronic pain without the risk of being crippling or addictive.

Chronic pain is very difficult to manage, and currently available medications are limited due to serious side effects. Opioids such as morphine and fentanyl are the gold standard for short-term pain relief but they cannot effectively treat chronic pain due to the risks of addition, misuse, and overdose.

The results of the new study published in the journal Life Sciences AllianceA single injection of a precisely engineered neurotransmitter botulinum was shown to provide long-term relief in mouse models, without adverse effects.

The team, led by Professor Pazbek Davletov, Head of Biomedical Sciences, and Research Associate at Sheffield Charlotte Lees University, developed a new method for reconstituting Botox using Clostridium botulinum elements and created biologics with new properties, without unwanted toxic effects. .

By splitting the Botox into two separate parts, the team was able to produce them in a perfect elongated configuration, and then put them back together in Lego-like fashion.

Professor Davletov, from the University of Sheffield’s School of Biological Sciences, said: “Currently, painkillers can only temporarily relieve chronic pain and often have unwanted side effects.”

“A single injection of a new, non-blocking inhibitor at the site of pain can provide pain relief for several months in humans, and this now needs to be tested.”

“We hope that the engineered drug can improve the quality of life for the millions of people around the world who suffer from chronic pain.”

“The promising results led to the transfer of the technology to US-based biopharmaceutical start-up Neuresta. The Neuresta team is now working on neuronal blockers specifically designed for various neurological conditions using the new bonding technology.”

Professor Davletov added, “This new biopharmaceutical development program could make it possible to produce a variety of Botox-like drugs in a safer and more economical way.”

While current Botox injections and similar Dysport injections can effectively paralyze muscles, the biopharmaceutical preparation Botulinum Prolonged Blocks nerves associated with pain without causing muscle paralysis.

It shows a woman rubbing her shoulder
Chronic pain is very difficult to manage, and currently available medications are limited due to serious side effects. The image is in the public domain

Botox holds great promise for clinical applications, but its paralytic activity has been a stumbling block in pain relief thus far.

The team showed that the newly modified neurotoxin is a non-paralyzing neuroblocker in collaborative preclinical studies at the Universities of Sheffield, Reading and University College London.

This method can allow for a form of chronic pain relief that can last up to one injection of Botox — about four to five months — potentially helping up to 20 percent of the population thought to be living with chronic pain.

Dr Maria Mayaro, from the University of Reading, said, “People with chronic pain need new options to control their symptoms. They need safer and more effective drugs.”

“These new botulinum molecules are effective in reducing pain-like behavior in human pain models. We believe this approach could open the way for the development of pain therapy to improve the quality of life of the millions of people who suffer from chronic pain.”

About this news Find pain

author: press office
source: University of Sheffield
communication: Press Office – University of Sheffield
picture: The image is in the public domain

Original search: open access.
“Constructs of a Novel Botulinum Neurotoxin for the Treatment of Chronic Pain” by Charlotte Lees et al. Life Sciences Alliance

a summary

Builds a new botulinum neurotoxin to treat chronic pain

Chronic pain affects one in five people in the human population, with few treatment options available. Botulinum neurotransmitter (BoNT) can provide long-term pain relief by inhibiting the local release of neuropeptides and neurotransmitters, but its highly paralyzing nature limited its analgesic potential.

Recent advances in protein engineering have raised the possibility of manufacturing non-paralyzing botulinum molecules for translation to people suffering from pain.

However, the synthesis of these molecules, via several synthetic steps, has been challenging. Here, we describe a simple platform for the safe production of botulinum particles for the treatment of pain caused by nerve injury.

We produced two copies of isopeptide-bound BoNT from separate fragments of botulinum using an isopeptide-binding system. Although both molecules cleaved their natural substrate, SNAP25, in sensory neurons, the structurally elongated iBoNT did not cause motor deficits in mice. We have shown that a non-paralyzed elongated iBoNT targets specific cutaneous nerve fibers and provides sustained pain relief in a rat nerve injury model.

Our results show that new botulinum particles can be produced in a simple and safe manner and be useful in the treatment of neuropathic pain.

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