In a recent adavancement , researchers at the University of California, Davis have developed monoclonal antibodies that could help treat chronic pain. The goal is to develop a monthly, non-addictive pain reliever that can be used in place of opioids.
The project is led by Vladimir Yarov-Yarovoy and James Trimmer, professors in the Department of Physiology and Membrane Biology at UC Davis School of Medicine. They’ve assembled an interdisciplinary team that includes several of the same experts who are working to convert tarantula venom into a painkiller.
Yarov-Yarovoy and Trimmer were honored earlier this year with a $1.5 million grant from the National Institutes of Health‘s HEAL initiative, a determined attempt to accelerate the development of scientific solutions to the country’s opioid crisis.
People can become dependent on opioids because of chronic pain. According to the CDC National Center for Health Statistics, there will likely be 107,622 drug overdose deaths in the United States in 2021, up from an expected 93,655 deaths in 2020.
“Recent breakthroughs in structural and computational biology – the use of computers to understand and model biological systems – have set the stage for the application of new approaches to developing antibodies as superior therapeutic candidates to treat chronic pain,” said Yarov-Yarovoy, who Principal Investigator for the award.
“Monoclonal antibodies are the fastest growing sector of the pharmaceutical industry and have many advantages over traditional small molecule drugs,” said Trimmer. Small molecule drugs are drugs that can easily enter cells. They are widely used in medicine.
Trimmer’s lab has produced thousands of different monoclonal antibodies for various purposes over many years, but this is the first attempt to create antibodies for pain relief.
Monoclonal antibodies are already being used to treat migraines
Although it may seem very futuristic, the Food and Drug Administration has already approved monoclonal antibodies to treat and prevent migraines. These new drugs act on a migraine-associated protein called calcitonin gene-related peptide.
The project at UC Davis has a different goal — specific ion channels in nerve cells known as voltage-gated sodium channels. The channels are like “pores” on the nerve cell.
In response to the US opioid crisis, researchers at UC Davis are trying to make monoclonal antibodies that may help fight chronic pain. The research is funded by a $1.5 million grant from the National Institutes of Health’s HEAL initiative. Photo credit: UC Davis Health
“Nerve cells are responsible for transmitting pain signals in the body. Voltage-gated sodium ion channels in nerve cells are the most important pain transmitters,” explains Yarov-Yarovoy. “Our goal is to develop antibodies that bind to these specific transmission sites at the molecular level, inhibit their activity and stop the transmission of pain signals.”
Researchers are focusing on three specific sodium ion channels implicated in pain: NaV1.7, NaV1.8 and NaV1.9.
Their goal is to create antibodies that fit into each of these channels like a key into a lock. This targeted approach aims to prevent the channels from sending pain signals but not interfere with other signals being sent through the nerve cells.
But the researchers are excited about the potential of this new approach. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and acetaminophen need to be taken several times a day to relieve pain. Opioid painkillers are often taken daily and are addictive.
However, monoclonal antibodies can circulate in the bloodstream for more than a month before they are eventually cleared by the body. The researchers assume that the patient would inject himself with the painkiller with monoclonal antibodies once a month.
“For chronic pain patients, this is exactly what you need,” Yarov-Yarovoy said. “They are in pain, not for days, but for weeks and months. The expectation is that the circulating antibodies can provide sustained pain relief for weeks.”
The study was funded by the National Institutes of Health.