During the pandemic, doctors used infusions of monoclonal antibodies — antibodies made in a lab — to help patients fight off COVID-19 infections. Now researchers from the University of California in Davis are trying to create monoclonal antibodies that can help in the fight against chronic pain. The goal is to develop non-addictive monthly pain medications that can replace opioids.
Vladimir Yarov-Yaravoy and James Trimmer, professors in the Department of Physiology and Membrane Biology at the University of California, Davis School of Medicine, are leading the project. They assembled a multidisciplinary team that includes many of the same researchers who are also trying to turn tarantula venom into pain reliever.
Earlier this year, Yarov-Yarovoy and Trimmer received a $1.5 million grant from the National Institutes of Health’s HEAL initiative, an active effort to accelerate scientific solutions to end the nation’s opioid crisis.
People can become addicted to opioids because of chronic pain. CDC National Center for Health Statistics showed an estimate 107,622 drug overdose deaths in the United States in 2021, an increase of nearly 15% from the 93,655 deaths estimated in 2020.
“The latest breakthroughs in structural and computational biology— using a computer for understanding and modeling biological systems— laid the groundwork for new approaches to develop antibodies as better therapeutic candidates for the treatment of chronic pain,” said Yarav-Yaravoy, principal investigator of the award.
“Monoclonal antibodies are the fastest growing sector of the pharmaceutical industry and have many advantages over classical small molecule drugs,” Trimmer said. Small molecule drugs are drugs that easily enter cells. They are widely used in medicine.
Trimmer’s lab has created thousands of different ones monoclonal antibodies for various purposes over the years, but this is the first attempt to create antibodies aimed at relieving pain.
Monoclonal antibodies are already used for migraine
While this may sound very futuristic, the Food and Drug Administration has already approved monoclonal antibodies for the treatment and prevention of migraine. These new drugs work on a protein associated with migraines called calcitonin gene-related peptide.
A project at the University of California, Davis, has a different goal — specific ion channels nerve cells known as voltage-gated sodium channels. Channels are like “pores” on a nerve cell.
“Nerve cells are responsible for transmitting pain signals in the body. Voltage-gated sodium ion channels in nerve cells are key transmitters of pain,” Yarav-Yaravoy explained. “We aim to create antibodies that will bind to these specific transmission sites molecular levelslowing down their activity and stopping the transmission of pain signals.’
The researchers focused on three specific sodium ion channels associated with pain: NaV1.7, NaV1.8 and NaV1.9.
Their goal is to create antibodies that can fit into each of these channels like a key in a lock. This targeted approach aims to ensure that the channels do not send pain signals, but do not interfere with other signals sent through the nerve cells.
The problem is that the structures of the three channels they are trying to block are incredibly complex.
The software helps you create virtual models
To solve this problem, they turn to programs called Rosetta and AlphaFold. Using Rosetta, the researchers are developing complex virtual models of the proteins and analyzing which ones best match the neural channels NaV1.7, NaV1.8 and NaV1.9. With AlphaFold, researchers independently test proteins developed by Rosetta.
Once they’ve identified a few promising proteins, they’ll create antibodies that can then be tested on lab-created nerve tissue. Human trials will take years.
But researchers are excited about the potential of this new approach. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and acetaminophen, should be taken several times a day to relieve pain. Opioid pain medications are often taken daily and carry the risk of addiction.
Monoclonal antibodies, however, can circulate in the blood for more than a month before they are finally broken down by the body. The researchers believe that the patient will self-inject pain-relieving monoclonal antibodies once a month.
“For patients with chronic painthis is exactly what you need – said Yarav-Yaravoy. – They are experiencing pain, not for days, but weeks and months. Circulating antibodies are expected to provide persistence pain relief weeks”.
Additional team members include Bruno Correia of EPFL, Stephen Waxman of Yale University, William Schmidt of EicOsis, and Heike Wolff, Thean Griffith, Karen Wagner, John T. Sack, David J. Copenhaver, Scott Fishman, Daniel J. Tancredi, Hai Nguyen, Phuong Tran Nguyen, Diego Lopez Mateos, and Robert Stewart of the University of California, Davis.
Citation: Can monoclonal antibodies replace opioids in chronic pain? (2022, September 22) Retrieved September 22, 2022, from https://medicalxpress.com/news/2022-09-monoclonal-antibodies-opioids-chronic-pain.html
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