Stimulating the vagus nerve reveals medical potential for a range of health conditions
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The US Food and Drug Administration (FDA) has granted approval for a vagus nerve stimulation device aimed at treating rheumatoid arthritis. This marks the first time a device like this has been authorized for an autoimmune disorder, opening possibilities for broader medical uses.
The small, tablet-sized device is surgically placed alongside the vagus nerve, which consists of nerve fibers connecting the brain to vital organs. It automatically administers electrical pulses that stimulate the nerves and help reduce inflammation for up to a decade.
Rheumatoid arthritis, similar to other autoimmune disorders, leads to excessive inflammation, causing the body to mistakenly attack its own tissues, resulting in pain, swelling, and potential organ damage. Treatment typically involves strong anti-inflammatory medications that suppress the immune system, increasing vulnerabilities to infections and cancer. Nearly 75% of rheumatoid arthritis patients express dissatisfaction with current therapies and have discontinued them due to adverse side effects.
In clinical trials, 242 participants with moderate to severe rheumatoid arthritis were tested, showing that about 35% of those receiving vagus nerve stimulation for 12 weeks experienced at least a 20% reduction in symptoms compared to only 24% in the placebo group. Less than 2% faced serious side effects, and none developed severe infections.
“Utilizing a safe computer chip as an alternative to expensive, minimally effective medications with significant side effects presents an appealing option for many patients,” remarked Kevin Tracy from the Feinstein Institute of Medicine in New York. He originated the device approximately two decades ago while working with Setpoint Medical, a US medical technology firm that is no longer operational.
This approval signifies a pivotal advancement toward potentially treating various inflammation-related ailments, including heart failure, diabetes, and neurodegenerative disorders such as Parkinson’s disease, through vagus nerve stimulation. Stavros Zanos at the Feinstein Medical Institute emphasizes that SetPoint Medical’s device is already being evaluated in clinical trials for conditions like multiple sclerosis and inflammatory bowel disease.
ohRan Knowles, a British teenager with a severe form of epilepsy called Lennox-Gastaut syndrome, became the first person to try the new brain implant last October, with astonishing results: his daytime seizures reduced by 80 percent.
“The device has had a huge impact on my son's life as he no longer falls and injures himself like he used to,” said his mother, a consultant paediatric neurosurgeon at Great Ormond Street Hospital in London (Gosh), who implanted the device. She added that there has been a huge improvement in her son's quality of life as well as his cognitive abilities. He is more alert and outgoing.”
Oran's neurostimulator is implanted under the skull and sends constant electrical signals deep into the brain with the aim of blocking the abnormal impulses that cause seizures.The implant, called Picostim, is about the size of a cell phone battery, is charged through headphones and works differently during the day and at night.
“The device has the ability to record from the brain, to measure brain activity, and we can use that information to think about how to improve the effectiveness of the stimulation that children are receiving,” says Tisdall. “What we'd really like to do is to make this treatment available on the NHS.”
As part of the trial, three children with Lennox-Gastaut syndrome will be fitted with the implant in the coming weeks, with a full trial planned for 22 children early next year. If the trial is successful, academic sponsors Ghosh and University College London plan to apply for regulatory approval.
Tim Denison, a professor of engineering science at the University of Oxford and co-founder and chief engineer at Amber Therapeutics, a London-based company that developed the implant in collaboration with the university, hopes that the device will be available on the NHS and around the world within the next four to five years.
The technology is one of a number of neural implants being developed to treat a range of conditions, including brain tumors, chronic pain, rheumatoid arthritis, Parkinson's disease, incontinence and tinnitus. These devices are more sophisticated than traditional implants in that they not only decode the brain's electrical activity but also control it, and this is where Europe is racing against the US to develop life-changing technology.
The latest generation of brain implants can not only detect brain activity but also control it. Photo: UCL
Amber isn't the only company working on brain implants to treat epilepsy. California-based Neuropace has developed a device that responds to abnormal brain activity and has been cleared by US regulators for use by people aged 18 and over. But the battery is not rechargeable and must be surgically replaced after a few years. Other devices are implanted in the chest with wires running to the brain that must be reinserted as the child grows.
When most people think of brain chips, they think of Neuralink, another California-based startup from Elon Musk that just implanted a brain chip in a second patient with a spinal cord injury. The device uses tiny wires thinner than a human hair to capture signals from the brain and translate them into actions.
The first recipient, Noland Arbaugh, was in January and is paralyzed from the neck down. Some of the wires had shifted and the implant needed to be adjusted. The implant allows Arbaugh to control a mouse cursor on a computer screen with his mind, as if he were watching a movie. Star Wars A Jedi who “uses the Force.”
Other US companies, such as Syncron, backed by Bill Gates and Jeff Bezos, have also recently implanted brain-computer interfaces (BCIs) in people who cannot move or speak.
But scientists say these implants simply decode electrical signals. In contrast, a number of companies in the U.S., Britain and Europe, like Amber, are working on so-called “BCI therapy,” or modulating signals in deep brain stimulation to treat disease. Amber's implants are also being used in academic trials for Parkinson's disease, chronic pain and multiple system atrophy, a condition that gradually damages nerve cells in the brain. The company is also sponsoring an early trial in Belgium to treat incontinence, with promising results.
Professor Martin Tisdall led the team that gave Oran Noorsson, who suffers from severe epilepsy, the implant last October. Photo: UCL
A different kind of technology will be tested in humans in clinical trials starting in a few weeks, using the first brain implant made from graphene, a “miracle material” discovered 20 years ago at the University of Manchester.
Medical teams at Salford Royal Infirmary will implant a device with 64 graphene electrodes into the brains of patients with glioblastoma, a fast-growing form of brain cancer. The device will stimulate and read neural activity with high precision, to spare other parts of the brain while removing the cancer. The implant will be removed after surgery.
“We use this interface to map out where the glioblastoma is and then remove it. [cut it out] “Without affecting areas of function such as language or cognition,” says Carolina Aguilar, co-founder and CEO of InBrain Neuroelectronics, the Barcelona-based company that developed the implant in collaboration with the Catalan Institute of Nanoscience and Nanotechnology and the University of Manchester.
Traditionally, platinum and iridium have been used in implants, but graphene, made from carbon, is ultra-thin, harmless to human tissue, and can be decoded and modulated very selectively.
InBrain plans to conduct clinical trials of similar artificial intelligence-powered implants in people with speech disorders caused by Parkinson's disease, epilepsy and stroke.
Professor Costas Kostarellos, head of nanomedicine at the University of Manchester, co-founder of InBrain and principal investigator on the glioblastoma trial, says the company's goal is to “develop more intelligent implantable systems”.
Equipped with AI, the device, with 1,024 electrical contacts, “will help provide optimal treatment for each patient without the neurologist having to program all those contacts individually, as they do today,” he says.
InBrain has partnered with German pharmaceutical company Merck to use its graphene device to stimulate the vagus nerve, which controls many bodily functions including digestion, heart rate and breathing, to treat severe chronic inflammatory, metabolic and endocrine diseases such as rheumatoid arthritis.
Galvani Bioelectronics, founded in 2016 by the UK's second-largest pharmaceutical company GSK and Alphabet's Verily Life Sciences, has a pioneering treatment that treats rheumatoid arthritis by stimulating the splenic nerve. Galvani has begun clinical trials with patients in the UK, US and the Netherlands, with first results expected within the next 6-12 months.
Bioelectronics, which combines biological sciences and electrical engineering, is a market worth $8.7 billion today and is predicted to reach more than $20 billion (£15 billion) by 2031. According to Verified Market Research:The field focuses on the peripheral nervous system, which transmits signals from the brain to organs and from organs to the brain. When brain-focused neuromodulation and BCIs are added, Aguilar believes the overall market could be worth more than $25 billion.
While U.S. neuromodulation companies are making waves with devices targeting chronic pain and sleep apnea, a growing number of European startups are also working on the technology. MintNeuro, a spinout from Imperial College London, Working on developing next-generation chips The company is developing an implant that can be combined into a smaller implant and has partnered with Amber. With the support of an Innovate UK grant, its first project will be to develop an implant to treat mixed urinary incontinence.
Geneva-based Neurosoft has developed a device that uses a thin metal film attached to stretchy silicon – soft enough to put less pressure on the brain and blood vessels – to target severe tinnitus, which affects 120 million people worldwide.
“Tinnitus begins with ear damage, typically caused by loud noise, but it can also cause changes in the wiring of the brain, making it effectively a neurological disorder,” said Nicholas Batsikouras, the company's chief executive officer.
Founded in 2009 by 13 neurosurgeons, neurologists, engineers and other scientists from the Policlinico Research Center and the University of Milan, Neuronica has developed a rechargeable deep brain neurostimulator that can be used to treat Parkinson's disease. The device provides closed-loop stimulation and adapts moment-to-moment to the patient's condition, and is currently being tested on patients.
“Europe and the UK can compete head-to-head with the US when it comes to getting treatments onto the NHS and distributing them around the world,” Denison said. “It's a fair competition and we're going to give it our all.”
Osteoarthritis affects 530 million people worldwide
Puwadol Jaturautchai/Shutterstock
Drug delivery nanoparticles may be useful in treating osteoarthritis. In mice with signs of symptoms, a single injection of the particles relieved pain for several months.
Osteoarthritis is the most common form of arthritis and is approximately 530 million people worldwide. It occurs when the cartilage that cushions bones breaks down, causing joint stiffness and pain. Treatment options for this condition are limited, and there is no treatment to prevent cartilage degeneration.
Previous research has shown that a drug called pazopanib may help reduce osteoarthritis pain. However, the effect only lasts for a few days.So Heejeong Im Sampeng University of Illinois at Chicago and colleagues have developed a method of administration that extends release.
The researchers encapsulated pazopanib within nanoparticles that have already been approved by the U.S. Food and Drug Administration to deliver other drugs. They then injected the nanoparticles into the knees of 16 mice, and found that half of them had early signs of osteoarthritis, and half had advanced signs. The same number of animals received a dummy injection of nanoparticles without pazopanib.
Because it is difficult to assess joint pain in animals, the researchers used the widely accepted idea that individuals experiencing pain, such as joint pain, also become more sensitive to physical touch. and instead focused on rodent sensitivities.
Immediately after treatment, the researchers assessed how quickly the mice removed one paw from the uncomfortable hot plate. Mice with early or advanced osteoarthritis took significantly longer to remove their paws when given pazopanib rather than a dummy injection, suggesting that pazopanib nanoparticles rapidly reduced joint pain. I did. The researchers then repeated the hot plate test and found similar effects after two months in the advanced osteoarthritis group and after three months in the early osteoarthritis group. This means that pazopanib nanoparticles provide effective pain relief over several weeks. Animals treated with pazopanib also had less cartilage degeneration, indicating that nanoparticles may slow the progression of osteoarthritis.
But just because a treatment works in mice doesn't mean it will work in humans, Sampen says. The researchers plan to explore other ways to assess pazopanib's analgesic properties in animals. One approach, the researchers say, is to analyze how people walk and use their limbs to make sure the drug reduces joint pain.
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