Summary: A newly developed extended-release botulinum neurotoxin can relieve chronic pain symptoms without causing addiction or nerve damage that leads to paralysis.
Source: University of Sheffield
A team of scientists from the Universities of Sheffield, Reading and University College London (UCL) and US-based biopharmaceutical company Neuresta have created a new, extended botulinum neurotoxin that can relieve chronic pain without the risk of paralysis or addiction
Chronic pain is very difficult to manage, and currently available medications are limited by dangerous side effects. Opioids such as morphine and fentanyl are the gold standard for short-term pain relief but they do not effectively treat chronic pain due to the risk of addiction, abuse and overdose.
Findings of the new study, published in the journal Life Science Allianceshow that a single injection of precisely engineered botulinum neurotoxin provides long-term relief in rat models, without adverse effects.
The team, led by Professor Bazbek Davletov, Chair of Biomedical Science, and Research Associate Charlotte Leese from the University of Sheffield, developed a new method of reconstructing Botox by using elements of Clostridium botulinum and create a biopharmaceutical with new properties, without unwanted toxic effects. .
By splitting the Botox into two separate parts, the team was able to get them into an optimally elongated configuration, and then put them back together in a Lego-like fashion.
Professor Davletov, from the University of Sheffield’s School of Biosciences, said, “Currently, painkillers can only relieve chronic pain temporarily and often have unwanted side effects.”
“A single injection of the new nonparalytic blocker at the site of pain can potentially relieve pain for months in humans and this now needs to be tested.”
“We hope that engineered medicine can improve the quality of life for millions of people around the world who suffer from chronic diseases.”
“The promising results led to the transfer of the technology to a US-based biopharmaceutical startup company Neuresta. The Neuresta team is now working on neuronal blockers tailored for various neurological conditions using the new binding strategy.
Professor Davletov added, “This new program of biopharmaceutical development could make it possible to produce different drugs like Botox in a safer and more economical way.”
While current Botox and similar Dysport injections can effectively paralyze muscles, the extended botulinum biopharmaceutical blocks the nerves associated with the disease without causing muscle paralysis.
Botox holds great promise for clinical applications, but its paralytic activity has been an obstacle for pain relief until now.
The team showed that their newly engineered neurotoxin is a non-paralyzing neuronal blocker in preclinical collaborative studies at the Universities of Sheffield, Reading and UCL.
The procedure could potentially allow a form of chronic pain relief that could last as long as a single Botox injection—around four to five months—potentially helping up to 20 percent of the population thought to be living with chronic illness
said Dr. Maria Maiaru, from the University of Reading, “People with chronic diseases need new options for managing 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 that this method may open the way for developing pain treatment to improve quality of the lives of millions of people living with chronic illness.”
About this disease research news
Author: Press Office
Source: University of Sheffield
Contact: Press Office – University of Sheffield
Image: The image is in the public domain
Original Research: Open access.
“New botulinum neurotoxin constructs for the treatment of chronic pain” by Charlotte Leese et al. Life Science Alliance
Abstract
New botulinum neurotoxin constructs for the treatment of chronic pain
Chronic pain affects one in five people throughout human society, with few treatment options available. Botulinum neurotoxin (BoNT) can provide long-term pain relief by inhibiting the local release of neuropeptides and neurotransmitters, but its paralytic nature limits its analgesic potential.
Recent advances in protein engineering have raised the possibility of synthesizing non-paralyzing botulinum molecules for delivery to patients.
However, the synthesis of these molecules, through several synthetic steps, has been difficult. Here, we describe a simple platform for the safe production of botulinum molecules for the treatment of pain caused by nerve injury.
We made two versions of isopeptide-bonded BoNT from separate botulinum moieties using the isopeptide bonding system. Although both molecules eliminated their natural substrate, SNAP25, in sensory neurons, the structurally extended iBoNT did not cause motor deficits in mice. We show that non-paralytic elongated iBoNT targets specific cutaneous nerve fibers and provides long-lasting pain relief in a rat nerve injury model.
Our results show that novel botulinum molecules can be produced in a simple and safe manner and be useful for the treatment of neuropathic pain.
