An experimental painkiller could be the key to solving the opioid epidemic
Known as 'SBI-810,' the drug avoids the 'high' that is tied to addiction to the pain-relieving drugs.
The need for such a breakthrough is great, even as U.S. overdose deaths decline. Recent data showed they fell by 30,000 last year, but more than 80,000 people still died from the drugs. Drug overdose deaths have been increasing in the U.S. since the 1990s, mostly due to the use of opioids.
'What makes this compound exciting is that it is both analgesic and non-opioid,' Dr. Ru-Rong Ji, an anesthesiology and neurobiology researcher who directs the Duke Anesthesiology Center for Translational Pain Medicine, said in a statement. Well-known drugs like Advil and Tylenol are analgesic drugs, which are also known as painkillers.
Ji was the senior author of the related Department of Defense- and National Institutes of Health-funded research, which was published on Monday in the journal Cell.
Duke said the drug has undergone trials in mice, working well on its own. When used in combination with opioids, it made them more effective at lower doses, the authors said.
Opioids increase levels of dopamine in the brain, which is often referred to as the 'happy hormone.' In turn, that dopamine and opioids work together to generate the high. But, over time, the body needs higher doses to feel the same effect.
Like opioids, SBI-810 works on the nervous system to relieve pain. The experimental compound is designed to target a receptor – the brain receptor neurotensin receptor 1 – found on the spinal cord and nerve cells that function to transmit information to the central nervous system.
The difference between opioids and SBI-810 is that Duke's drug takes a more focused approach than opioids. Instead of flooding multiple cellular pathways at the same time, the researcher noted, it activates only one specific pain-relief pathway that avoids that euphoric high.
Furthermore, the researchers say it can prevent the common side effects that often force patients to need stronger and more frequent doses of opioids, including constipation and tolerance.
It also outperformed the nerve pain drug gabapentin, and didn't cause sedation or memory problems often reported with that drug. Gabapentin is the seventh most commonly prescribed medication nationally.
The authors have compared SBI-810 to oliceridine, a newer type of opioid used in hospitals. However, they found that SBI-810 worked better in some situations.
It also effectively relieved pain from surgical incisions, bone fractures, and nerve injuries better than some existing painkillers, reducing signs of discomfort on a mouse's face.
They hope to do human trials soon and have locked in multiple patients.
Although the drug is still in early development, the authors said it could be a safer option for treating both short-term and chronic pain for those recovering from surgery or living with diabetic nerve pain. More than a third of Americans are living with chronic pain.
'The receptor is expressed on sensory neurons and the brain and spinal cord,' Ji added. 'It's a promising target for treating acute and chronic pain.'
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National Geographic
13 hours ago
- National Geographic
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Goose-beaked whales hold the record for the deepest dive of any mammal. Researchers want to learn their secrets to develop new drugs for human diseases. Goose-beaked whales (Ziphius cavirostris) hold the record for deepest dive of any marine mammal, and researchers hope that examining how these animals manage their oxygen thousands of feet underwater could one day yield medications that help humans. Photograph By Vincent Legrand/AGAMI Photo Agency/Alamy Whale sightings are never guaranteed, and goose-beaked whales are particularly hard to spot because they spend 90 percent of their time submerged. So when Jillian Wisse and her team position their boat in the right spot and the whales surface, it's a feat. During their field expeditions off the North Carolina coast, sometimes they can even cruise close enough to take tissue samples and appreciate the rake-like scratches that the animals acquire from mating behaviors, social play, and dominance displays. 'They look like the English bulldogs of the whale world. I love seeing them,' says Wisse, a behavioral physiologist at Duke University. Formerly known as Cuvier's beaked whales, goose-beaked whales dive deeper than any other known mammal and are found in most of the world's oceans. The elusive animals regularly dive down to around 3,300 feet and hunt for 20 to 40 minutes straight. Their deepest dive on record is 9,816 feet, and the longest known dive lasted 222 minutes. For comparison, blue whales only reach around 1,640 feet with dive durations around 10 to 20 minutes, and the best human divers tap out at records of 831 feet and 25 minutes. To achieve such impressive dives, goose-beaked whales' bodies have adapted to survive levels of hypoxia or oxygen deprivation that could easily kill a human. Wisse's expeditions are part of a Duke project that aims to understand these deep ocean adaptations in cetaceans, the group that includes whales and bottlenose dolphins. Hypoxia plays a role in health conditions from stroke to cancer, and the researchers' ultimate goal is to apply the findings from the marine mammals to develop treatments that could one day help humans, too. (These divers have evolved an ability to use oxygen more efficiently.) The Duke project is one of many research efforts worldwide that uses whales as models for understanding human diseases. Most of what we know about how deep diving animals handle low oxygen comes from beached whales and seals, which spend more time at the surface and are smaller and easier to study. But the Duke team focuses on getting samples from living whales and dolphins, especially extreme divers like goose-beaked whales, to figure out what's happening in their cells that allows them to survive low oxygen environments. First, the researchers need to get their hands on whale tissues. 'It's hard to get data from whales—they are very hard to get close to,' notes Nicola Quick, a marine scientist and one of the project's leaders. Skin is the most accessible tissue in live whales, though they are not fully representative of what happens inside their bodies, says Wisse who also leads the Duke University's project. From live whales, scientists use a dart to punch out a piece of skin from the thick blubber or fat layer. 'Imagine you took a number two pencil, pulled the eraser out, poked yourself, and pulled it away. That's essentially what's happening,' Wisse explains. Skin cells are multiplied in the lab, exposed to very low oxygen levels like what whales experience during deep dives, and studied. With stranded or beached animals, sampling gets a little bit easier—tissues from skin as well as heart, lung, muscle, and even the brain are simply cut off and brought to the lab. The project is ongoing, but they already have some early results from skin samples of live and stranded goose-beaked whales from the Western North Atlantic. Even under low oxygen conditions, whale skin cells seem to consume oxygen at high levels, while skin cells of dolphins, cows, and humans reduced their oxygen consumption when oxygen was limited. Compared to humans, goose-beaked whales also carry differences in genes that regulate how mitochondria, the power plants of the cell, produce energy. What all this means is that whales have genetically-encoded adaptations that enable them to continue producing energy even when oxygen is extremely limited, while humans—and probably, other land-dwelling mammals lack these adaptations. These findings about the cellular adaptations in whales build on what researchers previously knew about the physiological adaptations whales have for oxygen consumption during deep dives, Wisse says. More blood and slower metabolism Studies of seals and dead whales have already revealed changes in how the animals' bodies function. Seals have about twice the blood volume of humans, carrying much more hemoglobin than we do, says Lars Folklow, an animal physiologist at the Arctic University of Norway. 'They would be caught in any blood doping test in the Olympics, for example,' chuckles Folklow, who researches hypoxia protection mechanisms in diving species. (How do diving seals know how long to hold their breath?) More blood volume means that the animals also have more hemoglobin, the protein that binds to oxygen in the blood and transports it to other organs. That means seals and other diving mammals have a very high capacity to store oxygen. They can surface with a blood oxygen content that is so low that we would lose consciousness if it was us, says Folklow. Estimates from beached sperm whales suggest that blood accounts for 20 percent of their body weight, compared to only seven to eight percent in humans. Whales also have high amounts of myoglobin, the oxygen-carrying protein in muscles, which helps them sustain at great depths for long durations. Previous research has also shown that whales can dramatically slow down their metabolism when they dive for extended periods of time. Their normal heart rate of 30 to 40 beats per minute at the surface plummets to less than 10 beats per minute during deep dives. The heart rate drop reduces the amount of blood flow and oxygen to non-critical areas like the digestive system, kidneys, and muscles. 'There is no need to run the kidneys at full speed or digest your latest meal while you are diving,' Folklow explains. Instead, the animals selectively perfuse more blood and oxygen to critical organs like the brain. 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Folklow says this could be due to divergent evolution in whales and seals, a phenomenon where two related species independently develop different strategies to combat the same environmental challenge. Besides binding with oxygen, neuroglobin also prevents oxidative stress, which can damage cells. Either of these neuroglobin functions could be helping whales, says Folklow, and it's difficult to narrow down to one of them without running experiments with live brain tissues, the kind of sample that is near-impossible to access. (Whales could one day be heard in court—and in their own words.) What this means for human medicine Despite the experimental challenges, marine mammal researchers hope that their work on hypoxia could help humans overcome health conditions where oxygen is a factor, like stroke, prolonged anesthesia, COVID-19, and cancer. 'One thing we're interested to know is how marine mammals deal with inflammation when diving to such extreme depths,' says Jason Somarelli, a medical oncologist at Duke University and one of the leaders of the whale project. In humans, low-oxygen states are usually tied to inflammation, ultimately leading to tissue damage or death. But deep diving mammals have evolved sophisticated ways to carefully control and manage inflammatory responses, including carrying natural anti-inflammatory substances in their blood. Scientists are still working to fully understand how exactly these protective mechanisms work, but Somarelli suspects that marine mammals must have uncoupled their oxygen sensing response from inflammatory response. If this is true, figuring out how the animals achieve this feat could help identify molecules that a medicine can lock on to and uncouple these signals in humans, says Somarelli. For now, drugs inspired by whale biology are only hypothetical. But hypoxia researchers aren't the only ones interested. Other labs are studying bowhead whales' resilience to age-related diseases like cancer and exceptional longevity. Their super-efficient DNA repair systems could potentially be used to develop treatments for human diseases. Scientists are also studying dementia-like brain changes in toothed whales to better understand Alzheimer's disease. Meanwhile, Wisse continues to snag skin biopsies in hopes of further probing the cellular pathways that help whale cells deal with hypoxia. Finding goose-beaked whales is still like searching for a needle in a haystack for her. When a whale surfaces for a minute and a half, she accelerates her boat to get parallel to the animal and darts to remove a pencil eraser-sized piece of blubber layer that bounces off and floats. The whale then swims away. 'But my favorite moment is when they kind of turn and look back at me straight into my eye,' Wisse says. 'They know what's going on.'
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A family in Santa Clarita has finally received a call saying their immunocompromised baby will be getting a life-saving implant. For over a year, the Landrons have self-quarantined to protect their daughter, Syanne, who was born without a thymus gland, meaning she has no immunity. The family has completely changed their lives, deciding to work from home and homeschool their other children to keep her safe. They were told she'd need an implant and in May, Syanne was approved to get the surgery from a healthy baby who is undergoing surgery. However, Duke University is the only facility in the U.S. to perform the implant. The family told CBS Los Angeles that they recently received the call they've been waiting for from the medical team at Duke. Syanne will soon be getting her life-saving implant. It is unclear exactly when she will have the surgery, but her family is happy their prayers have finally been answered.
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