A therapy that has risen to prominence during the Covid pandemic and has even been used to treat Donald Trump could help alleviate the deadly epidemic of opioid overdose in the United States, scientists hope.
Monoclonal antibodies – or anti-virus proteins made in the laboratory – fight infections by preventing the virus from invading cells and reducing the risk of being hospitalized with the disease.
Now, scientists are on the way to using this treatment to relieve chronic pain, which forces arthritis and cancer sufferers to take multiple pills a day for months, potentially creating an addiction.
They are designing an antibody that could bind to nerve cells to prevent them from sending persistent pain signals to the brain.
Research at the University of California, Davis is still in its infancy and it will be years before it hits hospital or pharmacy shelves.
But scientists hope that within a few years they will have developed a non-addictive monthly injection that will serve as an alternative to opioids such as morphine, which are used as a last resort for patients with chronic pain usually after surgery.
It could also be used to help people on nonsteroidal anti-inflammatory drugs (NSAIDs) such as arthritis and cancer patients, who may have taken multiple pills a day for months.
Overdose deaths in the United States hit a record high of nearly 108,000 last year, a 15% increase from the number in 2020 – although the pandemic has made it more difficult to obtain legal drugs and illegal.
Of the 108,000 overdose deaths last year, 85% involved an opioid like fentanyl or a prescription drug.
Scientists at the University of California, Davis hope to develop a non-addictive alternative to opioid painkillers. The steps required to build the alternative are shown above. They’ve already completed the first, identifying the channels they need to block on cells to stop pain signals. But they say it will take years to develop the treatment
Scientists hope to develop a non-opioid painkiller using monoclonal antibody technology. Right: Trump pictured at Walter Reed Army Medical Center after testing positive for Covid in October 2020. He received an experimental monoclonal antibody treatment to help fight his infection
The graph above shows the number of overdose deaths involving opioids and is from the Centers for Disease Control and Prevention (CDC). It reveals that the number of deaths reached an all-time high in 2020, the latest year for which figures are available. Opioid overdose deaths account for approximately 80% of all overdose deaths
Dr Vladimir Yarov-Yarovoy (above) is one of the lead scientists in the study taking place at UC Davis.
How would the treatment work?
– Scientists use advanced computer programs to design complex virtual models of proteins.
– They are analyzing which proteins would best fit three specific ion channels in nerve cells, which are responsible for transmitting pain signals in the body.
– They create antibodies that bind to these three specific channels on nerve cells, inhibiting their activity and preventing them from sending pain signals.
– A patient with chronic pain would receive a monthly infusion of monoclonal antibodies.
Source: University of California, Davis
Monoclonal antibody treatments were not born out of the pandemic. The first monoclonal antibody was approved by federal regulators in 1986 for use in preventing kidney transplant rejection.
But scientists have advanced the technology so much in recent years that the therapy has become a very effective tool in preventing cases of severe Covid illness.
In October 2020, Donald Trump was treated with a then-experimental antibody cocktail made by Regeneron after testing positive for Covid.
He has been credited with the former president’s rapid recovery which saw him hold several rallies in the final weeks of the White House race – just days after testing positive on October 2.
The treatment worked by binding to the virus’ spike protein which it uses to invade cells, stopping an infection in its tracks.
Now, UC Davis researchers aim to create antibodies that can bind to three specific channels on nerve cells that send pain signals to the brain.
“Recent breakthroughs in structural and computational biology – the use of computers to understand and model biological systems – have paved the way for applying new approaches to creating antibodies as superior therapeutic candidates to treat chronic pain. said Dr. Vladimir Yarov-Yarovoy, the lead researcher.
By blocking pain transmitters, scientists hope it will relieve chronic pain for up to a month – about the lifespan of antibodies in the body.
“For chronic pain patients, this is exactly what you need,” Dr. Yarov-Yarovoy said.
“They feel pain, not for days, but for weeks and months.”
He added: “Circulating antibodies are expected to provide sustained pain relief for weeks.”
The team is currently designing the antibodies, which will then be tested on human tissue in the lab before moving on to animal trials.
The treatment – which would be administered intravenously – is years away from reaching humans.
But it could be a game-changer because one in five Americans suffer from chronic pain.
UC Davis researchers received $1.5m (£1.4m) in grants last April from the National Institutes of Health, the federal government’s principal agency for biomedical and public health research, to fund the project.
One of the main challenges will be to reproduce the exact structure of these three very complex channels. Computer programs are used to overcome this. One such program, known as Rosetta, allows researchers to create three-dimensional virtual protein models and determine which fits perfectly into all three channels (shown).
The goal, Dr. Yarov-Yarovoy said, is to create antibodies in the lab that fit into three specific voltage-gated sodium ions in nerve cells like keys in locks.
One of the main challenges will be to reproduce the exact structure of these three very complex channels.
Computer programs are used to overcome this.
One such program, known as Rosetta, allows researchers to create virtual three-dimensional protein models and determine which one fits perfectly into all three channels.
The AlphaFold serves as a fact-checker, re-analyzing Rosetta’s protein designs to ensure the dimensions are correct.
The experiment, if successful, will prove instrumental in curbing the ongoing crisis of opioid addiction fueled by many physicians who prescribe aggressively and underestimate the risk of becoming dependent on drugs.
More than 260,000 Americans have died from an overdose of prescription opioid medications in the past two decades, according to CDC data.
Overdose deaths involving opioids have been on a relatively steady slope since 2010, when they were around 21,000. That rate rose to 47,600 in 2017 and remained high at nearly 69,000 in 2020.
Fentanyl, a synthetic opioid, caused more overdoses than any other drug in 2021, resulting in more than 71,000 deaths, up 23% from the previous year.