Sodium valproate is an effective drug for epilepsy, but its consumption is not recommended during pregnancy
Miljan Zivković/Shutterstock
The drug rapamycin may prevent the epilepsy drug sodium valproate from causing developmental problems during pregnancy.
Sodium valproate is used to treat epilepsy, bipolar disorder, and sometimes migraines. Although effective, it is not recommended during pregnancy as it can cause birth defects such as spina bifida and lifelong learning disabilities.
Giovanni Pietrogrande Researchers from the University of Queensland in Australia wanted to understand why sodium valproate could have such an effect. So they used stem cells to create mini-spinal cords called organoids in the lab. These mimic the spine of a fetus during early pregnancy.
When organoids were exposed to sodium valproate, their cells changed in ways that may be associated with risk of congenital disease.
The researchers looked for reasons for this and found that activity in one of the cell's signaling pathways, called mTOR, indicates that cells are aging. This is a process in which cells stop growing but do not die, but instead continue to release chemicals that can cause inflammation.
Rapamycin, which was initially developed as an immunosuppressant but has some promise for anti-aging effects, also targets the mTOR pathway.
In another experiment, researchers exposed a new set of spinal cord organoids to a combination of sodium valproate and rapamycin and found that no aging occurred. They then replicated this test in zebrafish larvae and found that the cells similarly did not undergo senescence and showed no signs of the changes that occur when exposed to sodium valproate alone.
Rather than doctors discontinuing sodium valproate if an epileptic patient is pregnant or may become pregnant, someday doctors may be able to prevent the negative effects of sodium valproate by combining it with rapamycin. Pietro Grande says. Human studies are needed to make this recommendation.
Frank Vajda The University of Melbourne says sodium valproate is “a critically important drug and the single most effective treatment for generalized seizures, where abnormal electrical activity begins in both halves of the brain at the same time.”
“I think this is a very important paper that could lead to a return to the level of importance that this drug had before its side effects were discovered,” he says.
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.”
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