UC Davis researchers seek to develop a non-addictive, monthly painkiller.
During the pandemic, doctors employed infusions of monoclonal antibodies (lab-made antibodies) to help patients fight COVID-19 infections. University of California, Davis researchers are now attempting to develop monoclonal antibodies that may aid in the treatment of chronic pain. The objective is to create a monthly non-addictive pain medication that can be used instead of opioids.
The project is led by Vladimir Yarov-Yarovoy and James Trimmer, professors in the Department of Physiology and Membrane Biology at the UC Davis School of Medicine. They’ve established an interdisciplinary team that includes several of the same experts that are working on turning tarantula venom into a pain medication.
Yarov-Yarovoy and Trimmer were awarded a $1.5 million grant earlier this year by the National Institutes of Health’s HEAL Initiative, a determined effort to hasten the development of scientific solutions to the country’s opioid crisis.
People can become addicted to opioids due to chronic pain. According to the CDC National Center for Health Statistics, there will likely be 107,622 drug overdose deaths in the US in 2021, up from an expected 93,655 deaths in 2020.
“Recent breakthroughs in structural and computational biology — using computers to understand and model biological systems — have set the stage for applying new approaches to create antibodies as superior therapeutic candidates to treat chronic pain,” said Yarov-Yarovoy, the principal investigator for 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 can easily enter cells. They are widely used in medicine.
Trimmer’s lab has created thousands of different monoclonal antibodies for various purposes over many years, but this is the first attempt to generate antibodies aimed at pain relief.
Monoclonal antibodies are already being used for migraine
Although it may seem very futuristic, the Food and Drug Administration has already approved monoclonal antibodies to treat and prevent migraine. These new medications act on a migraine-associated protein called calcitonin gene-related peptide.
The project at UC Davis has a different target—specific ion channels in nerve cells known as voltage-gated sodium channels. The channels are like “pores” on the nerve cell.
“Nerve cells are responsible for transmitting pain signals in the body. Voltage-gated sodium ion channels in nerve cells are the key transmitters of pain,” explained Yarov-Yarovoy. “We aim to create antibodies that will bind to these specific transmission sites at the molecular level, inhibiting their activity and stopping the transmission of pain signals.”
The researchers are 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 into a lock. This targeted approach is intended to stop the channels from sending pain signals but not interfere with other signals sent through the nerve cells.
The challenge is that the structures of the three channels they are attempting to block are incredibly complex.
Software programs help create virtual models
To address this, they are turning to software programs called Rosetta and AlphaFold. With Rosetta, the researchers are designing complex virtual models of proteins and analyzing which ones might best fit the NaV1.7, NaV1.8, and NaV1.9 nerve channels. With AlphaFold, the researchers independently validate proteins designed by Rosetta.
Once they identify several promising proteins, they will create antibodies that can then be tested on lab-created neural tissue. Human testing would be years away.
But the researchers are excited by the potential of this new approach. Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and acetaminophen must be taken several times per day to relieve pain. Opioid pain medications are often taken daily and run the risk of addiction.
Monoclonal antibodies, however, can circulate in the bloodstream for more than a month before they are eventually broken down by the body. The researchers anticipate that the patient would self-inject the monoclonal antibody pain medication once a month.
“For patients with chronic pain, that’s exactly what you need,” Yarov-Yarovoy said. “They experience pain, not for days, but weeks and months. The expectation is that the circulating antibodies will be able to provide sustained pain relief for weeks.”
The study was funded by the National Institutes of Health.
News
Scientists Just Found DNA’s Building Blocks in Asteroid Bennu – Could This Explain Life’s Origins?
Japanese scientists detected all five nucleobases — building blocks of DNA and RNA — in samples returned from asteroid Bennu by NASA’s OSIRIS-REx mission. NASA’s OSIRIS-REx mission brought back 121.6 grams of asteroid Bennu, unveiling nitrogen-rich organic matter, including DNA’s essential [...]
AI-Designed Proteins – Unlike Any Found in Nature – Revolutionize Snakebite Treatment
Scientists have pioneered a groundbreaking method to combat snake venom using newly designed proteins, offering hope for more effective, accessible, and affordable antivenom solutions. By utilizing advanced computational techniques and deep learning, this innovative [...]
New nanosystem offers hope for improved diagnosis and treatment of tongue cancer
A pioneering study has unveiled the Au-HN-1 nanosystem, a cutting-edge approach that promises to transform the diagnosis and treatment of tongue squamous cell carcinoma (TSCC). By harnessing gold nanoparticles coupled with the HN-1 peptide, [...]
Global Trust in Science Is Stronger Than Expected – What’s Next?
A landmark global survey conducted across 68 countries has found that public trust in scientists remains robust, with significant support for their active involvement in societal and political matters. The study highlights the public’s [...]
Microplastics in the bloodstream may pose hidden risks to brain health
In a recent study published in the journal Science Advances, researchers investigated the impact of microplastics on blood flow and neurobehavioral functions in mice. Using advanced imaging techniques, they observed that microplastics obstruct cerebral blood [...]
AI Surveillance: New Study Exposes Hidden Risks to Your Privacy
A new mathematical model enhances the evaluation of AI identification risks, offering a scalable solution to balance technological benefits with privacy protection. AI tools are increasingly used to track and monitor people both online [...]
Permafrost Thaw: Unleashing Ancient Pathogens and Greenhouse Gases
Permafrost is a fascinating yet alarming natural phenomenon. It refers to ground that remains frozen for at least two consecutive years. Mostly found in polar regions like Siberia, Alaska, and Canada, permafrost plays a [...]
Frequent social media use tied to higher levels of irritability
A survey led by researchers from the Center for Quantitative Health at Massachusetts General Hospital and Harvard Medical School has analyzed the association between self-reported social media use and irritability among US adults. Frequent [...]
Australian oysters’ blood could hold key to fighting drug-resistant superbugs
Protein found in Sydney rock oysters’ haemolymph can kill bacteria and boost some antibiotics’ effectiveness, scientists discover An antimicrobial protein found in the blood of an Australian oyster could help in the fight against [...]
First U.S. H5N1 Death Sparks Urgency: Scientists Warn Bird Flu Is Mutating Faster Than Expected
A human strain of H5N1 bird flu isolated in Texas shows mutations enabling better replication in human cells and causing more severe disease in mice compared to a bovine strain. While the virus isn’t [...]
AI Breakthrough in Nanotechnology Shatters Limits of Precision
At TU Graz, a pioneering research group is leveraging artificial intelligence to drastically enhance the way nanostructures are constructed. They aim to develop a self-learning AI system that can autonomously position molecules with unprecedented precision, potentially [...]
How Missing Sleep Lets Bad Memories Haunt Your Mind
Research reveals that a lack of sleep can hinder the brain’s ability to suppress unwanted memories and intrusive thoughts, emphasizing the importance of restful sleep for mental health. Sleep deprivation has been found to [...]
WHO issues new warning over ‘mystery virus’ and calls for return of COVID restrictions
The World Health Organization (WHO) has called for the reinstatement of restrictions implemented during the COVID-19 pandemic as cases of human metapneumovirus (HMPV) continue to surge. While hospitals in China are overwhelmed with positive [...]
A Breath Away From a Cure: How Xenon Gas Could Transform Alzheimer’s Treatment
A breakthrough study highlights Xenon gas as a potential game-changer in treating Alzheimer’s disease, demonstrating its ability to mitigate brain damage and improve cognitive functions in mouse models. A forthcoming clinical trial aims to test its [...]
False Memories Under Fire: Surprising Science Behind What We Really Recall
New research challenges the ease of implanting false memories, highlighting flaws in the influential “Lost in the Mall” study. By reexamining the data from a previous study, researchers found that many supposed false memories [...]
Born Different? Cambridge Scientists Uncover Innate Sex Differences in Brains
Cambridge researchers found that sex differences in brain structure exist from birth, with males having more white matter and females more grey matter, highlighting early neurodiversity. Research from the Autism Research Centre at the University [...]
