Tag Archives: epilepsy

Tiny ‘Keyhole’ Discovery May Transform Treatment Of Pain And Epilepsy

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A new set of studies by scientists at the Vlaams Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel (VUB) and KU Leuven has uncovered how minute molecular changes can dramatically alter the way the body processes pain and responds to certain epilepsy drugs.

Published in the journal Nature Communications, the research focuses on the TRPM3 ion channel — a protein known to play a key role in sensing pain and linked to rare neurological disorders and epilepsy.

A ‘lock-and-key’ mechanism at molecular level

Researchers identified what they describe as a tiny binding site — a “molecular keyhole” — within the TRPM3 channel. Even slight alterations in this pocket can completely change how the channel behaves.

“If you have the mirror image of your key or you make a very small change to the key or to the keyhole, suddenly the door might open or close,” said Thomas Voets, co-lead of the study.

The team examined isosakuranetin, a plant-derived compound often explored for blocking TRPM3 activity. The molecule exists in two mirror-image forms, known as S and R.

“We discovered that the active form of isosakuranetin is R, not S,” said researcher Bahar Bazeli. “R is a potent inhibitor of the channel, while S is ineffective.”

Why some treatments fail

The study goes further, showing that mutations found in some patients can alter this keyhole — effectively changing how drugs interact with the channel.

“Any small change in this pocket can affect the direction of the effect and also the efficacy,” Bazeli explained. “You can turn an antagonist into an agonist and vice versa.”

This means that in certain patients, drugs designed to block pain signals could become ineffective — or even produce the opposite effect. According to the researchers, patients with specific TRPM3 mutations “shouldn’t use the drug everyone else uses” as it may cause side effects without benefits.

Link to severe facial pain

A parallel study published in Cell Reports Medicine examined the role of TRPM3 in trigeminal neuralgia — a condition widely regarded as one of the most painful disorders.

The research found that nerve injury and inflammation significantly increase TRPM3 activity, making pain-sensing neurons hyperactive.

“Trigeminal neuralgia is one of the worst pain syndromes. People call it the suicide disease because it’s so painful,” Voets said, adding: “We show that inhibiting TRPM3 works surprisingly well in animal models.”

Genetic analysis also revealed that certain TRPM3 variants are more common in patients with the condition, suggesting a biological reason why standard treatments fail in some cases.

Toward personalised medicine

Taken together, the findings point to a shift toward more targeted therapies. By understanding how individual variations in the TRPM3 “keyhole” affect drug response, scientists say treatments could be tailored to each patient.

“Knowing exactly how a molecule fits in this lock helps a lot with developing better and more specific drugs,” Voets said. “We are now working on keys that fit even better.”

The researchers are now focusing on designing mutation-specific inhibitors — a step that could pave the way for personalised therapies for chronic pain, epilepsy and related neurological disorders.

The bigger picture

The discovery underscores how even the smallest molecular differences can have wide-ranging clinical consequences. It also highlights why a one-size-fits-all approach to treatment often fails in complex neurological conditions.

If translated into clinical practice, the “molecular keyhole” concept could mark a significant step toward precision medicine — where treatments are not just disease-specific, but tailored to the genetic profile of each patient.

 

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Now go for painless tattoos that can be self-administered, say Researchers

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Instead of sitting in a tattoo chair for hours enduring painful punctures, imagine getting tattooed by a skin patch containing microscopic needles. Researchers at the Georgia Institute of Technology have developed low-cost, painless, and bloodless tattoos that can be self-administered and have many applications, from medical alerts to tracking neutered animals to cosmetics.

“We’ve miniaturized the needle so that it’s painless, but still effectively deposits tattoo ink in the skin,” said Mark Prausnitz, principal investigator on the paper. “This could be a way not only to make medical tattoos more accessible, but also to create new opportunities for cosmetic tattoos because of the ease of administration.”

Tattoos are used in medicine to cover up scars, guide repeated cancer radiation treatments, or restore nipples after breast surgery. Tattoos also can be used instead of bracelets as medical alerts to communicate serious medical conditions such as diabetes, epilepsy, or allergies.

Various cosmetic products using microneedles are already on the market — mostly for anti-aging — but developing microneedle technology for tattoos is new. Prausnitz, a veteran in this area, has studied microneedle patches for years to painlessly administer drugs and vaccines to the skin without the need for hypodermic needles.

tattoo/en.wikipedia.org

“We saw this as an opportunity to leverage our work on microneedle technology to make tattoos more accessible,” Prausnitz said. “While some people are willing to accept the pain and time required for a tattoo, we thought others might prefer a tattoo that is simply pressed onto the skin and does not hurt.”

Transforming Tattooing

Tattoos typically use large needles to puncture repeatedly into the skin to get a good image, a time-consuming and painful process. The Georgia Tech team has developed microneedles that are smaller than a grain of sand and are made of tattoo ink encased in a dissolvable matrix.

“Because the microneedles are made of tattoo ink, they deposit the ink in the skin very efficiently,” said Li, the lead author of the study.

In this way, the microneedles can be pressed into the skin just once and then dissolve, leaving the ink in the skin after a few minutes without bleeding.

Tattooing Technique

Although most microneedle patches for pharmaceuticals or cosmetics have dozens or hundreds of microneedles arranged in a square or circle, microneedle patch tattoos imprint a design that can include letters, numbers, symbols, and images. By arranging the microneedles in a specific pattern, each microneedle acts like a pixel to create a tattoo image in any shape or pattern.

The researchers start with a mold containing microneedles in a pattern that forms an image. They fill the microneedles in the mold with tattoo ink and add a patch backing for convenient handling. The resulting patch is then applied to the skin for a few minutes, during which time the microneedles dissolve and release the tattoo ink. Tattoo inks of various colors can be incorporated into the microneedles, including black-light ink that can only be seen when illuminated with ultraviolet light.

Prausnitz’s lab has been researching microneedles for vaccine delivery for years and realized they could be equally applicable to tattoos. With support from the Alliance for Contraception in Cats and Dogs, Prausnitz’s team started working on tattoos to identify spayed and neutered pets, but then realized the technology could be effective for people, too.

The tattoos were also designed with privacy in mind. The researchers even created patches sensitive to environmental factors such as light or temperature changes, where the tattoo will only appear with ultraviolet light or higher temperatures. This provides patients with privacy, revealing the tattoo only when desired.

A magnified view of a microneedle patch with green tattoo ink/photo:Georgia Tech

The study showed that the tattoos could last for at least a year and are likely to be permanent, which also makes them viable cosmetic options for people who want an aesthetic tattoo without risk of infection or the pain associated with traditional tattoos. Microneedle tattoos could alternatively be loaded with temporary tattoo ink to address short-term needs in medicine and cosmetics.

Microneedle patch tattoos can also be used to encode information in the skin of animals. Rather than clipping the ear or applying an ear tag to animals to indicate sterilization status, a painless and discreet tattoo can be applied instead.

“The goal isn’t to replace all tattoos, which are often works of beauty created by tattoo artists,” Prausnitz said. “Our goal is to create new opportunities for patients, pets, and people who want a painless tattoo that can be easily administered.”

 

Covid raises brain complications, epilepsy risks in kids: Report

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A latest study has shown that not only adults but children who suffered from Covid-19 are prone to risk of cognitive deficit, insomnia, ischaemic stroke, nerve or psychotic disorders and epilepsy or seizures  months later.

The post-Covid risk trajectories differed in children compared with adults, said the team of researchers at the University of Oxford.  Published in The Lancet Psychiatry journal, the findings are based on a  data of 185,748 children found that post-Covid risk trajectories differed in children compared with adults.

In the six months after SARS-CoV-2 infection, children were not at an increased risk of mood or anxiety disorders. However, they developed “an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures”.

Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days). “Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern,” said the study.

A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures.

Just after the emergence of the delta variant, increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate.

“With Omicron, there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar,” revealed the study.

The observational study extracted data from the ‘TriNetX’ electronic health records network, an international network of de-identified data from health care records of approximately 89 million patients collected from hospital, primary care, and specialist providers from the US, Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan.

New Technique Developed to Detect Epilepsy Brain Region for Surgery

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Researchers have identified a unique way to detect epileptic brain tissue that causes seizures.

The chemical biomarker can be detected noninvasively using a technique called magnetic resonance spectroscopy to help doctors to precisely identify small regions of abnormal brain tissue in early-stage epilepsy patients. This can help in surgery of epileptic brain regions for therapeutic removal without the need for additional surgery, said researchers.

Epilepsy affects about one percent of people worldwide and it is characterized by unpredictable seizures that occur when groups of neurons in the brain abnormally fire in unison. About 30 percent of epilepsy patients don’t respond to drugs and surgery is only the option to remove areas of the brain associated with epileptic activity.

“One of the biggest challenges in epilepsy is in diagnosis,” said Dr. Jeffrey Loeb, John S. Garvin Chair and head of neurology and rehabilitation in the University of Illinois at Chicago College of Medicine and corresponding author on the study.

Current non-invasive techniques can’t detect epileptic areas of the brain smaller than approximately eight to 10 square centimeters, so many early-stage epilepsy patients often go undiagnosed and untreated.

“With this new biomarker, we should be able to detect very small regions of epileptic activity — smaller than a single square centimeter — and we do it noninvasively,” Loeb said.

The biomarker may soon make the need for surgery to identify epileptic regions of the brain for later removal obsolete. To locate these areas, surgeons implant electrodes across the surface of the brain that need to stay in place for many days.

Dr. Jeffrey Loeb, John S. Garvin Chair and head of neurology and rehabilitation in the UIC College of Medicine. CREDIT Jenny Fontaine, UIC

Loeb and colleagues used a technique called magnetic resonance spectroscopy to identify the metabolomic signature of epileptic versus non-epileptic brain tissues removed from nine patients who underwent invasive electrical brain monitoring as part of their epilepsy surgery. Magnetic resonance spectroscopy can detect compounds associated with cellular metabolism. As part of this therapeutic surgery, both epileptic and nearby regions with less or no epileptic electrical activity were also removed.

Loeb and colleagues scanned both types of tissue with a powerful 11.7 Tesla magnetic resonance spectroscopy machine at Wayne State University in Detroit. They found that tissue with high levels of epileptic electrical activity was low in lactate and had higher levels of creatine, phosphocreatine and choline, suggestive of abnormal metabolism.

When they looked at these tissues in the lab, they saw that it had increased vascularization compared to tissue with low or no epileptic electrical activity. Genetic analysis of the same tissue regions revealed higher activation of genes associated with vascularization and altered metabolic states.

“Previous studies have used magnetic resonance spectroscopy to look at single metabolites in epileptic brain tissue, but ours is the first to use high strength magnets to look at multiple metabolites simultaneously,” Loeb said. “When combined with our genomic and histological data from these same samples, the biomarker profile was not only highly specific for epileptic brain tissues, but also revealed an abnormal metabolic and vascular state that could underlie the epileptic condition.”

The reason behind the abnormal metabolic profile in epileptic tissue remains unknown and needs to be studied further, said Loeb. “These are areas of the brain where large populations of neurons are firing often, and this uses up a lot of energy, so it’s not surprising that we see an altered metabolic profile with a massive expansion of blood vessels.”

The findings are reported in the journal Epilepsia.