Posts Tagged GABA

[WEB PAGE] Neurotransmitters: What they are, functions, and psychology

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[WEB PAGE] What are the benefits of increased GABA levels in the brain?

Gamma-aminobutyric acid (GABA) is a neurotransmitter, or chemical messenger, in the brain. It blocks specific signals in the central nervous system, slowing down the brain. This provides a protective and calming effect on the brain and body.

The body produces GABA, and it may also be present in some fermented foods, such as kimchi, miso, and tempeh. These are not foods that most people include in their daily diets, so some people take GABA supplements to achieve the benefits.

In this article, we examine how increased levels of GABA may impact the brain and body, and whether taking GABA supplements could have the same benefits.

What is GABA?

a couple looking relaxed because of gaba activity.

GABA activity can relieve stress, reduce stress, and improve sleep.

GABA is a neurotransmitter that inhibits or slows the brain’s functions. This activity produces effects such as:

  • relieving anxiety
  • reducing stress
  • improving sleep
  • preventing brain damage

The brain naturally releases GABA at the end of a day to promote sleepiness and allow a person to rest. Some of the medications doctors prescribe to induce sleep and reduce anxiety may also increase the action of GABA.

Medical benefits of increased GABA

Some experts have suggested that increased levels of GABA may have benefits, but the evidence is not clear. According to a 2019 review, GABA has anti-microbial, anti-seizure, and antioxidant properties and may help treat and prevent conditions such as:

Medications to increase GABA

Doctors may prescribe medicines that increase the amount of GABA or stimulate the same neurotransmitters in the brain to treat some medical conditions, such as epilepsy.

For example, benzodiazepines (Valium, Xanax) act on many of the same neurotransmitter receptors as GABA. According to one study, people who have depression may have reduced GABA levels in the brain. The use of benzodiazepines may be beneficial in those instances.

Doctors also prescribe the medication gabapentin (Neurontin), which is chemically similar to GABA to reduce seizures and muscle pain.

However, doctors are not clear whether the therapeutic effects of these medications are related to their effect on GABA receptors or whether they work in other ways.

GABA as a supplement

a woman enjoying the benefits of taurine in an energy drink she is drinking

Many sports drinks contain GABA.

Some people take supplements of GABA for their supposed stress- and anxiety-relieving benefits.

The Food and Drug Administration (FDA) has approved GABA for use as a supplement and as a food additive. Manufacturers may add GABA to:

  • sports drinks
  • snack bars
  • chewing gum
  • candies, and more

Manufacturers produce GABA supplements by fermenting a form of lactic acid bacteria.

However, the FDA do not regulate dietary supplements in the same way as medications. Therefore, consumers should exercise caution as to where they purchase the product from and only buy from reputable vendors and companies.

How to use GABA supplements

Some people may take a supplement in pill form, while others may add it to foods, such as protein drinks.

Researchers have not established a daily recommended intake or a suggested upper limit for GABA. Anyone wanting to take GABA as a supplement should consider talking to their doctor first.

At present, there is not enough research to evaluate the possible side effects of taking GABA supplements. However, if a person does experience side effects that might be GABA-related, they should discontinue the use of the supplement and contact their doctor.

Benefits of taking GABA supplements

Some researchers have voiced concerns about the supposed positive benefits of taking GABA supplements. An article in the journal Frontiers in Psychology notes that experts remain unclear whether GABA offers real benefits or whether the effects that people report experiencing are a placebo response.

Other researchers do not believe that GABA supplements cross the blood-brain barrier, which they would have to do to have any effect on the body.

However, some studies report positive effects from taking GABA supplements. These include:

Enhanced thinking and task performance abilities

study from 2015 found that taking 800 milligrams (mg) of GABA supplementation per day enhanced a person’s ability to prioritize and plan actions. Although the study was small, involving just 30 healthy volunteers, it showed how GABA supplementation might promote enhanced thinking.

Stress reduction

An older study from 2012 found that taking 100 mg of GABA daily helped reduce stress due to mental tasks. Like many other studies related to GABA, the study was small and involved just 63 participants.

Workout recovery and muscle building

a man and a woman working out together outside.

GABA supplements may improve workout recovery and muscle building.

The participants performed the same resistance training exercises twice a week, and the researchers measured the results. The researchers found that the combination of whey protein and GABA increased levels of growth hormone compared to whey protein alone.

Although this was another small study, the researchers concluded that GABA supplements might help to build muscle and assist in workout recovery. They recommended that researchers conduct more studies.

Summary

GABA naturally plays an essential role in promoting sleep, relieving anxiety, and protecting the brain.

Scientists have not been able to prove the positive effects of GABA supplementation on a large scale, and their use may have limited effectiveness.

If a person has received a diagnosis for conditions such as depression, anxiety, or attention deficit hyperactivity disorder, they may wish to talk to their doctor about medically-proven treatment before taking GABA supplements.

via What are the benefits of increased GABA levels in the brain?

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[WEB PAGE] Neurotransmitters: What they are, functions, and psychology

Neurotransmitters are chemical messengers in the body. Their job is to transmit signals from nerve cells to target cells. These target cells may be in muscles, glands, or other nerves.

The brain needs neurotransmitters to regulate many necessary functions, including:

  • heart rate
  • breathing
  • sleep cycles
  • digestion
  • mood
  • concentration
  • appetite
  • muscle movement

The nervous system controls the body’s organs, psychological functions, and physical functions. Nerve cells, also known as neurons, and their neurotransmitters play important roles in this system.

Nerve cells fire nerve impulses. They do this by releasing neurotransmitters, which are chemicals that carry signals to other cells.

Neurotransmitters relay their messages by traveling between cells and attaching to specific receptors on target cells.

Each neurotransmitter attaches to a different receptor — for example, dopamine molecules attach to dopamine receptors. When they attach, this triggers action in the target cells.

After neurotransmitters deliver their messages, the body breaks down or recycles them.

Key types of neurotransmitters

a person pointing to neurotransmitters on a model of a brain.

Many bodily functions need neurotransmitters to help communicate with the brain.

Neurotransmitters have different types of action:

  • Excitatory neurotransmitters encourage a target cell to take action.
  • Inhibitory neurotransmitters decrease the chances of the target cell taking action. In some cases, these neurotransmitters have a relaxation-like effect.
  • Modulatory neurotransmitters can send messages to many neurons at the same time. They also communicate with other neurotransmitters.

Some neurotransmitters can carry out various functions, depending on the type of receptor that they are connecting to.

The following sections describe some of the best-known neurotransmitters.

Acetylcholine

Acetylcholine triggers muscle contractions, stimulates some hormones, and controls the heartbeat. It also plays an important role in brain function and memory. It is an excitatory neurotransmitter.

Low levels of acetylcholine are linked with issues with memory and thinking, such as those that affect people with Alzheimer’s disease. Some Alzheimer’s medications help slow the breakdown of acetylcholine in the body, and this can help control some symptoms, such as memory loss.

Having high levels of acetylcholine can cause too much muscle contraction. This can lead to seizures, spasms, and other health issues.

The nutrient choline, which is present in many foods, is a building block of acetylcholine. People must get enough choline from their diets to produce adequate levels of acetylcholine. However, it is not clear whether consuming more choline can help boost levels of this neurotransmitter.

Choline is available as a supplement, and taking high doses can lead to serious side effects, such as liver damage and seizures. Generally, only people with certain health conditions need choline supplements.

Dopamine

Dopamine is important for memory, learning, behavior, and movement coordination. Many people know dopamine as a pleasure or reward neurotransmitter. The brain releases dopamine during pleasurable activities.

Dopamine is also responsible for muscle movement. A dopamine deficiency can cause Parkinson’s disease.

A healthful diet may help balance dopamine levels. The body needs certain amino acids to produce dopamine, and amino acids are found in protein-rich foods.

Meanwhile, eating high amounts of saturated fat can lead to lower dopamine activity, according to research from 2015. Also, certain studies suggest that a deficiency in vitamin D can lead to low dopamine activity.

While there are no dopamine supplements, exercise may help boost levels naturally. Some research has shown that regular exercise improves dopamine signaling in people who have early stage Parkinson’s disease.

Endorphins

a laughing senior black woman.

The body may release endorphins during laughter.

One of the best-known ways to boost levels of feel-good endorphins is through aerobic exercise. A “runner’s high,” for example, is a release of endorphins. Also, research indicates that laughter releases endorphins.

Endorphins may help fight pain. The National Headache Foundation say that low levels of endorphins may play a role in some headache disorders.

A deficiency in endorphins may also play a role in fibromyalgiaThe Arthritis Foundation recommend exercise as a natural treatment for fibromyalgia, due to its ability to boost endorphins.

Epinephrine

Also known as adrenaline, epinephrine is involved in the body’s “fight or flight” response. It is both a hormone and a neurotransmitter.

When a person is stressed or scared, their body may release epinephrine. Epinephrine increases heart rate and breathing and gives the muscles a jolt of energy. It also helps the brain make quick decisions in the face of danger.

While epinephrine is useful if a person is threatened, chronic stress can cause the body to release too much of this hormone. Over time, chronic stress can lead to health problems, such as decreased immunity, high blood pressurediabetes, and heart disease.

People who are dealing with ongoing high levels of stress may wish to try techniques such as meditation, deep breathing, and exercise.

Anyone who thinks that their levels of stress could be dangerously high or that they may have anxiety or depression should speak with a healthcare provider.

Meanwhile, doctors can use epinephrine to treat many life threatening conditions, including:

  • anaphylaxis, a severe allergic reaction
  • asthma attacks
  • cardiac arrest
  • severe infections

Epinephrine’s ability to constrict blood vessels can decrease swelling that results from allergic reactions and asthma attacks. In addition, epinephrine helps the heart contract again if it has stopped during cardiac arrest.

GABA

Gamma-aminobutyric acid (GABA) is a mood regulator. It has an inhibitory action, which stops neurons from becoming overexcited. This is why low levels of GABA can cause anxiety, irritability, and restlessness.

Benzodiazepines, or “benzos,” are drugs that can treat anxiety. They work by increasing the action of GABA. This has a calming effect that can treat anxiety attacks.

GABA is available in supplement form, but it is unclear whether these supplements help boost GABA levels in the body, according to some research.

Serotonin

a father and son enjoying a sunny day on a hill.

Exposure to sunlight may increase serotonin levels.

Serotonin plays a role in depression and anxiety. Selective serotonin reuptake inhibitors, or SSRIs, can relieve depression by increasing serotonin levels in the brain.

Seasonal affective disorder (SAD) causes symptoms of depression in the fall and winter, when daylight is less abundant. Research indicates that SAD is linked to lower levels of serotonin.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) increase serotonin and norepinephrine, which is another neurotransmitter. People take SNRIs to relieve symptoms of depression, anxiety, chronic pain, and fibromyalgia.

Some evidence indicates that people can increase serotonin naturally through:

  • being exposed to bright light, especially sunlight
  • vigorous exercise

A precursor to serotonin, called 5-hydroxytryptophan (5-HTP), is available as a supplement. However, some research has found that 5-HTP is not a safe or effective treatment for depression and can possibly make the condition worse.

Summary

Neurotransmitters play a role in nearly every function in the human body.

A balance of neurotransmitters is necessary to prevent certain health conditions, such as depression, anxiety, Alzheimer’s disease, and Parkinson’s disease.

There is no proven way to ensure that neurotransmitters are balanced and working correctly. However, having a healthful lifestyle that includes regular exercise and stress management can help, in some cases.

Before trying a supplement, ask a healthcare provider. Supplements can interact with medications and may be otherwise unsafe, especially for people with certain health conditions.

Health conditions that result from an imbalance of neurotransmitters often require treatment from a professional. See a doctor regularly to discuss physical and mental health concerns.

 

via Neurotransmitters: What they are, functions, and psychology

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[WEB PAGE] How New Ketamine Drug Helps with Depression

Yale psychiatrists, pioneers of ketamine research, shed light on new FDA approval

An illustration of a woman suffering from depression who might be helped by esketamine

The FDA approval of esketamine gives doctors another valuable tool in their arsenal against depression—and offers new hope for patients no one had been able to help before. “This is a game changer,” says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country.

On March 5, the Food and Drug Administration (FDA) approved the first truly new medication for major depression in decades. The drug is a nasal spray called esketamine, derived from ketamine—an anesthetic that has made waves for its surprising antidepressant effect.

Because treatment with esketamine might be so helpful to patients with treatment-resistant depression (meaning standard treatments had not helped them), the FDA expedited the approval process to make it more quickly available. In one study, 70 percent of patients with treatment-resistant depression who were started on an oral antidepressant and intranasal esketamine improved, compared to just over half in the group that did not receive the medication (called the placebo group).

“This is a game changer,” says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country. The drug works differently than those used previously, he notes, calling ketamine “the anti-medication” medication. “With most medications, like valium, the anti-anxiety effect you get only lasts when it is in your system. When the valium goes away, you can get rebound anxiety. When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects,” he says.

And this is exactly what makes ketamine unique as an antidepressant, says Dr. Krystal.

However, as the nasal spray becomes available via prescription, patients have questions: How does it work? Is it safe? And who should get it? Read on for answers.

How do antidepressants work?

Research into ketamine as an antidepressant began in the 1990s with Dr. Krystal and his colleagues Dennis Charney, MD, and Ronald Duman, PhD, at the Yale School of Medicine. At the time (as is still mostly true today) depression was considered a “black box” disease, meaning that little was known about its cause.

One popular theory was the serotonin hypothesis, which asserted that people with depression had low levels of a neurotransmitter called serotonin. This hypothesis came about by accident—certain drugs given to treat other diseases like high blood pressure and tuberculosis seemed to drastically affect people’s moods. Those that lowered serotonin levels caused depression-like symptoms; others that raised serotonin levels created euphoric-like feelings in depressed patients. This discovery ushered in a new class of drugs meant to treat depression, known as selective serotonin reuptake inhibitors (SSRIs). The first one developed for the mass market was Prozac.

But eventually it became clear that the serotonin hypothesis didn’t fully explain depression. Not only were SSRIs of limited help to more than one-third of people given them for depression, but growing research showed that the neurotransmitters these drugs target (like serotonin) account for less than 20 percent of the neurotransmitters in a person’s brain. The other 80 percent are neurotransmitters called GABA and glutamate.

GABA and glutamate were known to play a role in seizure disorders and schizophrenia. Together, the two neurotransmitters form a complex push-and-pull response, sparking and stopping electrical activity in the brain. Researchers believe they may be responsible for regulating the majority of brain activity, including mood.

What’s more, intense stress can alter glutamate signaling in the brain and have effects on the neurons that make them less adaptable and less able to communicate with other neurons.

This means stress and depression themselves make it harder to deal with negative events, a cycle that can make matters even worse for people struggling with difficult life events.

Ketamine—from anesthetic to depression “miracle drug”

Interestingly, studies from Yale research labs showed that the drug ketamine, which was widely used as anesthesia during surgeries, triggers glutamate production, which, in a complex, cascading series of events, prompts the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, and gives patients the opportunity to develop more positive thoughts and behaviors. This was an effect that had not been seen before, even with traditional antidepressants.

“I think the interesting and exciting part of this discovery is that it came largely out of basic neuroscience research, instead of by chance,” says Gerard Sanacora, MD, PhD, a psychiatrist at Yale Medicine who was also involved in many of the ketamine studies. “It wasn’t just, ‘let’s try this drug and see what happens.’ There was increasing evidence suggesting that there was some abnormality within the glutamatergic system in the brains of people suffering from depression, and this prompted the idea of using a drug that targets this system.”

For the last two decades, researchers at Yale have led ketamine research by experimenting with using subanesthetic doses of ketamine delivered intravenously in controlled clinic settings for patients with severe depression who have not improved with standard antidepressant treatments. The results have been dramatic: In several studies, more than half of participants show a significant decrease in depression symptoms after just 24 hours. These are patients who felt no meaningful improvement on other antidepressant medications.

Most important for people to know, however, is that ketamine needs to be part of a more comprehensive treatment plan for depression. “Patients will call me up and say they don’t want any other medication or psychotherapy, they just want ketamine, and I have to explain to them that it is very unlikely that a single dose, or even several doses of ketamine alone, will cure their depression,” says Dr. Sanacora. Instead, he explains, “I tell them it may provide rapid benefits that can be sustained with comprehensive treatment plans that could include ongoing treatments with ketamine.  Additionally, it appears to help facilitate the creation new neural pathways that can help them develop resiliency and protect against the return of the depression.”

This is why Dr. Sanacora believes that ketamine may be most effective when combined with cognitive behavioral therapy (CBT). CBT is a type of psychotherapy that helps patients learn more productive attitudes and behaviors. Ongoing research, including clinical trials, addressing this idea are currently underway here at Yale.

A more patient-friendly version

The FDA-approved drug esketamine is one version of the ketamine molecule, and makes up half of what is found in the commonly used anesthetic form of the drug. It works similarly, but its chemical makeup allows it to bind more tightly to the NMDA glutamate receptors, making it two to five times more potent. This means that patients need a lower dose of esketamine than they do ketamine. The nasal spray allows the drug to be taken more easily in an outpatient treatment setting (under the supervision of a doctor), making it more accessible for patients than the IV treatments currently required to deliver ketamine.

But like any new drug, this one comes with its cautions. Side effects, including dizziness, a rise in blood pressure, and feelings of detachment or disconnection from reality may arise. In addition, the research is still relatively new. Studies have only followed patients for one year, which means doctors don’t yet know how it might affect patients over longer periods of time. Others worry that since ketamine is sometimes abused (as a club drug called Special K), there may be a downside to making it more readily available—it might increase the likelihood that it will end up in the wrong hands.

Also, esketamine is only part of the treatment for a person with depression. To date, it has only been shown to be effective when taken in combination with an oral antidepressant. For these reasons, esketamine is not considered a first-line treatment option for depression. It’s only prescribed for people with moderate to severe major depressive disorder who haven’t been helped by at least two other depression medications.

In the end, though, the FDA approval of esketamine gives doctors another valuable tool in their arsenal against depression—and offers new hope for patients no one had been able to help before.

To learn more, visit yalemedicine.org.

 

via How New Ketamine Drug Helps with Depression > Stories at Yale Medicine

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[Abstract] Role of Interhemispheric Cortical Interactions in Poststroke Motor Function

Background/Objective. We investigated interhemispheric interactions in stroke survivors by measuring transcranial magnetic stimulation (TMS)–evoked cortical coherence. We tested the effect of TMS on interhemispheric coherence during rest and active muscle contraction and compared coherence in stroke and older adults. We evaluated the relationships between interhemispheric coherence, paretic motor function, and the ipsilateral cortical silent period (iSP).

Methods. Participants with (n = 19) and without (n = 14) chronic stroke either rested or maintained a contraction of the ipsilateral hand muscle during simultaneous recordings of evoked responses to TMS of the ipsilesional/nondominant (i/ndM1) and contralesional/dominant (c/dM1) primary motor cortex with EEG and in the hand muscle with EMG. We calculated pre- and post-TMS interhemispheric beta coherence (15-30 Hz) between motor areas in both conditions and the iSP duration during the active condition.

Results. During active i/ndM1 TMS, interhemispheric coherence increased immediately following TMS in controls but not in stroke. Coherence during active cM1 TMS was greater than iM1 TMS in the stroke group. Coherence during active iM1 TMS was less in stroke participants and was negatively associated with measures of paretic arm motor function. Paretic iSP was longer compared with controls and negatively associated with clinical measures of manual dexterity. There was no relationship between coherence and. iSP for either group. No within- or between-group differences in coherence were observed at rest.

Conclusions. TMS-evoked cortical coherence during hand muscle activation can index interhemispheric interactions associated with poststroke motor function and potentially offer new insights into neural mechanisms influencing functional recovery.

 

via Role of Interhemispheric Cortical Interactions in Poststroke Motor Function – Jacqueline A. Palmer, Lewis A. Wheaton, Whitney A. Gray, Mary Alice Saltão da Silva, Steven L. Wolf, Michael R. Borich, 2019

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[WEB PAGE] When Will There Ever be a Cure for Epilepsy?

The three-pound organ that serves as command central for the human organism is certainly a marvel, just by virtue of the fact that the brain can appreciate its own awesomeness, even if it hasn’t quite perfected the flying car or even self-driving cars. Yet. Companies developing brain-computer interface technology are enabling humans to do things like send commands to computers by just flexing a bit of muscle. Still, there is much we don’t know about ourselves, no matter how much telepsychiatry we do. And that applies especially to medical conditions that affect the brain like epilepsy, a neurological condition for which there is no cure.

What is Epilepsy?

While most of us are probably familiar with some Hollywood-ized version of epilepsy in which someone starts flailing around after being hit by strobe lights on the disco floor, the reality is that epilepsy refers to a large group of neurological disorders that generally involve chronic, spontaneous seizures that vary greatly in how they manifest. The causes of epilepsy are also all over the place, from traumatic brain injuries and stroke to viral and bacterial infections to genetics.

A new set of classifications for epilepsy came out in 2017.

It is considered a brain disorder, according to the U.S. Centers for Disease Control (CDC), though some researchers have suggested it could be classified as a neurodegenerative disease like Parkinson’s or Alzheimer’s. In fact, there is research that suggests a genetic link between epilepsy and neurodegenerative diseases.

Not surprisingly, many of the companies developing therapies for neurodegenerative diseases are also working on treatments for epilepsy and vice versa. For example, a new, well-funded joint venture involving Pfizer (PFE) and Bain Capital called Cerevel, which we profiled in our piece on Parkinson’s disease, is also in advanced clinical trials for an epileptic drug. Its GABA A positive modulator drug candidate targets GABA (Gamma-Aminobutyric Acid) neurotransmitters that block impulses between nerve cells in the brain, helping keep the nervous system chill.

Impacts of Epilepsy

More than 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally, according to the World Health Organization (WHO). The CDC estimates about 3.4 million Americans live with the condition. Globally, an estimated 2.4 million people are diagnosed with epilepsy each year. Interestingly, the disorder seems to target those who can least afford it: WHO said nearly 80% of people with epilepsy live in low- and middle-income countries.

Impacts of epilepsy graphic

A 2015 study of a bunch of other studies that estimated the cost of epilepsy in the United States found that epilepsy-specific costs probably average out to about $10,000 based on the variety of ranges, which means epilepsy costs the United States healthcare system about $34 billion, though the numbers are widely debated. Conversely, WHO says low-cost treatments are available, with daily medication coming as cheaply as $5 per year, so another win for the U.S. healthcare system.

Treatments for Epilepsy

There are more than 20 antiepileptic drugs used to treat epilepsy, usually to help prevent or slow the occurrence of seizures. Other therapies include surgery and electroceutical treatment in which electrical stimulation is applied, usually to the vagus nerve, the longest cranial nerve in the body. While many find relief from one or more of these options, a third of those who suffer from epilepsy are not able to manage their seizures, according to the U.S. National Institutes of Health (NIH). Below we take a look at a range of innovative therapies designed to detect, stop, or find a cure for epilepsy.

Brain Stimulation Therapies

In our article on electroceutical treatments, we highlighted a London company called LivaNova (LIVN) that offers an implantable Vagus Nerve Stimulation (VNS) therapy that has been approved by the U.S. Food and Drug Administration (FDA) to help treat those with partial seizures who do not respond to seizure medications. A medical device company with a lengthy track record of returning value to investors, Medtronic (MDT) got FDA pre-market approval last year for its Deep Brain Stimulation (DBS) therapy for use in reducing partial-onset seizure for those who have proven to not respond to three or more antiepileptic medications. DBS therapy delivers controlled electrical pulses to an area in the brain called the anterior nucleus of the thalamus, which is part of a network involved in seizures. Yet another company offering a variation of brain stimulation therapy is NeuroPace, which markets its responsive neurostimulation device, or RNS system, as “the first and only brain-responsive neurostimulation system designed to prevent epileptic seizures at their source.”

Artificial Intelligence to Detect, Predict, and Control Epilepsy

The NIH is funding further research into implantable devices that can detect, predict, and stop a seizure before it happens, “working closely with industry partners to develop pattern-recognition algorithms,” which sounds an awful lot like artificial intelligence and machine learning will be at the forefront of some future diagnostics and treatment. AI in healthcare has been an ongoing theme around here, with a recent dive into AI and mental health. Back to AI and epilepsy: A group of neurologists at the Medical University of South Carolina developed a new method based on artificial intelligence to predict which patients will see success with surgical procedures designed to stop seizures. Sounds like a great idea to learn beforehand if it’s necessary to crack open your skull.

Click for company websiteA Boston area startup called Empatica, spun out from MIT in 2011, has raised $7.8 million for a smartwatch that detects possible seizures by monitoring subtle electrical changes across the surface of the skin. Other methods normally rely on electrical activity in the brain that tracks and records brain wave patterns called an electroencephalogram. Empatica’s seizure detection algorithm, on the other hand, can detect complex physiological patterns from electrodermal activity that is most likely to accompany a convulsive seizure. Psychology Today reportedthat the device, Embrace Watch, received FDA approval earlier this year for seizure control in children after getting the green light for the technology for adults in 2018.

The Empatica smartwatch can detect electrical currents in the skin to predict the onset of an epileptic seizure.

Click for company websiteAI and drug discovery for better epileptic drug candidates is yet another application that we would expect to see grow in the coming years. Silicon Valley-based startup System1 Biosciences raised $25 million last year, which included Pfizer among its dozen investors. System1 builds a sort of brain model for testing drug candidates using stem cell lines derived from patients with brain disease. The company uses robotic automation to develop these three-dimensional cerebral organoids, allowing it to generate huge datasets in a relatively short amount of time, then applying “advanced data analysis” (also AI?) to detect patterns that might match the characteristics of a neurological disease (what it refers to as deep phenotypes) such as epilepsy with novel treatments.

Cannabis for Controlling Seizures

We’ve written extensively about the suddenly booming hemp CBD market, noting that the FDA approved a CBD-based drug for epilepsy last year in our recent article on the best certified CBD oils on the market. However, we’ve only briefly profiled the company behind Epidiolex for treating rare forms of epilepsy, GW Pharmaceuticals (GWPH). Sporting a market cap just south of $5 billion, GW Pharmaceuticals has taken in about $300 million in post-IPO equity since our article, bringing total post-IPO equity funding to about $568 million. Aside from its successful epileptic drug, GW also developed the world’s first cannabis-based prescription medicine for the treatment of spasticity due to multiple sclerosis that is available in 25 countries outside the United States.

The forms of epilepsy that GW Pharmaceuticals can treat or can potentially treat.

Back on the epilepsy side, Epidiolex has been approved for two rare forms of epilepsy, with clinical trials underway for two more rare neurological disorders associated with seizures – tuberous sclerosis complex and Rett syndrome. Also in the pipeline is a drug dubbed CBDV (GWP42006) that’s also for treating epileptic seizures, though the results of a trial last year were not encouraging. The same compound is also being investigated for autism. Be sure to check out our article on Charlotte’s Web, a CBD company that came about because of epilepsy.

Helping Cells Get Their Vitamin K

Click for company websiteNeuroene Therapeutics is a small startup spun out of the Medical University of South Carolina that recently picked up $1.5 million in funding to tests its lead drug compounds, which are analogous to the naturally occurring form of vitamin K that is essential for brain health. In particular, the lab-developed vitamin K protects the integrity of the cell’s mitochondria, which serves as a sort of power plant for brain cells, helping the neural circuit fire better. Unfortunately, you can’t get the effect from simply eating a bowl of Special K each morning covered in an organic sugar substitute, so the company is developing a method to deliver the effects directly to the brain.

A Nasal Spray to Stop Seizures

Click for company websiteFounded in 2007 near San Diego, Neurelis licenses, develops, and commercializes treatments for epilepsy and other neurological diseases. It has raised $44.8 million in disclosed funding, most coming in a $40.5 million venture round last November. The company’s flagship product is called Valtoco, a formulation that incorporates diazepam, an existing drug used to control seizures and alcohol withdrawal, with a vitamin E-based solution that is delivered using a nasal spray when a sudden seizure episode occurs. The product uses an absorption enhancement technology called Intravail developed by another San Diego area company called Aegis Therapeutics that Neurelis acquired in December last year. Neurelis submitted Valtoco to the FDA for approval in September.

Conclusions

While many people with epileptic conditions can control their seizures with many of the current medications or other therapies available now, there’s a big chunk of the population that is living with uncertainty. Considering the strong link between neurological disorders like epilepsy and certain neurodegenerative disorders, expect to see some good synergies in the next five to 10 years, especially as automation and advanced analytics using AI start connecting the dots between genetics, biochemistry, and brain disorders.

via When Will There Ever be a Cure for Epilepsy? – Nanalyze

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[WEB SITE] A New Research for a better epilepsy treatment

A New Research for a better epilepsy treatment

About 1.2 percent of the population have active epilepsy. Although the majority of the people respond to anti-seizure medications, these medications may not work for every person. They may come with a risk of side effects. About 20 to 40 percent of patients with epilepsy continue to have seizures even after various anti-seizure medications.

Even when the drugs work, individuals may develop memory difficulties and depression. It may be due to the combination of the underlying seizure disorder and the drugs used to treat it.

A research team was led by Ashok K. Shetty. He is a Ph.D. professor at the Texas A&M College of Medicine. He is working on a permanent and better treatment for epilepsy. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).

“This publication by Dr. Shetty and his team is a step forward in treating incurable diseases of the brain,” said Darwin J. Prockop. He is an MD, Ph.D., the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine.

Working of excitatory and inhibitory neurons

Seizures are caused by the over-excitation of the excitatory neurons in the brain. Due to this overexcitation, they fire too much. And inhibitory neurons aren’t as abundant or aren’t effective at their optimum level.

Inhibitory neurons are required to stop the firing of excitatory neurons. Thus, the chief inhibitory neurotransmitter present in the brain is GABA, short for gamma-Aminobutyric acid.

Over the last decade, researchers have learned to generate induced pluripotent stem cells from normal adult cells, like a skin cell. Therefore, these stem cells can develop into nearly any type of cells in the body, including neurons which use GABA, called GABAergic interneurons.

“For this, transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy,” Shetty said.

The hippocampus is an area in the brain where seizures originate in temporal lobe epilepsy. It is also important for learning, mood, and memory. “Also, this region of brain functioned very well to overwhelm seizures. It even improves mental as well as mood functioning in the chronic epilepsy phase.”

Outcomes of the research

Additional testing exposed that the transplanted human neurons formed synapses with the excitatory neurons of the host. “They were also helpful for GABA and other markers of specific subclasses of inhibitory interneurons,” Shetty said.

“Another captivating aspect of this research is that transplanted human GABAergic neurons were found to be involved directly in controlling seizures. As silencing the transplanted GABAergic neurons caused an increased number of seizures.”

“One central aspect of the effort is that the similar cells can be attained from a patient.” This process, called autologous transplant, is patient specific. It means that there would be no rejection risk of the new neurons. And the person would not need anti-rejection drugs.

“However, we should make sure that we’re doing more good than harm,” Shetty said. “Going onward, we need to be certain that all the transplanted cells have turned into neurons. Because putting undifferentiated pluripotent stem cells could lead to tumors and other problems in the body.”

The epilepsy development often occurs after a head injury. That is why the Department of Defense is involved in funding the development of improved treatment and prevention options.

Treatment of other disorders

“Therefore, good research is essential before patients can be treated safely,” Prockop said. “But this study shows a technique through which patients can someday be treated with their own cells for the shocking epilepsy effects but possibly also other disorders like Parkinsonism and Alzheimer’s disease.”

Hence, Shetty advised that these tests were early interferences after the initial brain injury caused by status epilepticus. This is a state of continuous seizures in humans lasting more than five minutes.

The next phase is to understand if similar transplants would work for chronic epilepsy cases, mainly drug-resistant epilepsy. “Presently, there is no effective treatment for drug-resistant epilepsy. It is associated with memory problems, depression, and a death rate 5 to 10 times that of the general population,” he said.

“Hence, our findings propose that induced pluripotent stem cell-derived GABAergic cell therapy has the potential for providing a lifelong seizure control and releasing co-morbidities associated with epilepsy.”

 

via A New Research for a better epilepsy treatment

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[WEB SITE] Stem cell-derived neurons stop seizures and improve cognitive function

People with untreatable epilepsy may one day have a treatment: ‘Convincing’ their own cells to become the neurons they need

IMAGE

IMAGE: THIS IS ASHOK K. SHETTY. 
CREDIT: TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER.

About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.

A team led by Ashok K. Shetty, PhD, a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, associate director of the Institute for Regenerative Medicine and a research career scientist at the Olin E. Teague Veterans’ Medical Center, part of the Central Texas Veterans Health Care System, is working on a better and permanent treatment for epilepsy. Their results published this week in the Proceedings of the National Academy of Sciences (PNAS).

Seizures are caused when the excitatory neurons in the brain fire too much and inhibitory neurons–the ones that tell the excitatory neurons to stop firing–aren’t as abundant or aren’t operating at their optimal level. The main inhibitory neurotransmitter in the brain is called GABA, short for gamma-Aminobutyric acid.

Over the last decade, scientists have learned how to create induced pluripotent stem cells from ordinary adult cells, like a skin cell. These stem cells can then be coaxed to become virtually any type of cells in the body, including neurons that use GABA, called GABAergic interneurons.

“What we did is transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy,” Shetty said. The hippocampus is a region in the brain where seizures originate in temporal lobe epilepsy, which is also important for learning, memory and mood. “It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy.”

Further testing showed that these transplanted human neurons formed synapses, or connections, with the host excitatory neurons. “They were also positive for GABA and other markers of specialized subclasses of inhibitory interneurons, which was the goal,” Shetty said. “Another fascinating aspect of this study is that transplanted human GABAergic neurons were found to be directly involved in controlling seizures, as silencing the transplanted GABAergic neurons resulted in an increased number of seizures.”

“This publication by Dr. Shetty and his colleagues is a major step forward in treating otherwise incurable diseases of the brain,” said Darwin J. Prockop, MD, PhD, the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine. “One important aspect of the work is that the same cells can be obtained from a patient.” This type of process, called autologous transplant, is patient specific, meaning that there would be no risk of rejection of the new neurons, and the person wouldn’t need anti-rejection medication.

“We will need to make sure that we’re doing more good than harm,” Shetty said. “Going forward, we need to make sure that all of the cells transplanted have turned into neurons, because putting undifferentiated pluripotent stem cells into the body could lead to tumors and other problems.”

The development of epilepsy often happens after a head injury, which is why the Department of Defense is interested in funding the development of better treatment and prevention options.

“A great deal of research is required before patients can be safely treated,” Prockop said. “But this publication shows a way in which patients can someday be treated with their own cells for the devastating effects of epilepsy but perhaps also other diseases such as Parkinsonism and Alzheimer’s disease.”

Shetty cautioned that these tests were early interventions after the initial brain injury induced by status epilepticus, which is a state of continuous seizures lasting more than five minutes in humans. The next step is to see if similar transplants would work for cases of chronic epilepsy, particularly drug-resistant epilepsy. “Currently, there is no effective treatment for drug-resistant epilepsy accompanying with depression, memory problems, and a death rate five to 10 times that of the general population,” he said. “Our results suggest that induced pluripotent stem cell-derived GABAergic cell therapy has the promise for providing a long-lasting seizure control and relieving co-morbidities associated with epilepsy.”

 

via Stem cell-derived neurons stop seizures and improve cognitive function | EurekAlert! Science News

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[WEB SITE] Antiepileptic Drugs – Medscape

Overview

Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. In 1910, phenobarbital (PHB), which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. A number of medications similar to PHB were developed, including primidone.

In 1938, Houston Merrit and Tracy Putnam described animal models for screening multiple compounds for antiepileptic activity in the Journal of the American Medical Association. In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures.

In 1968, carbamazepine (CBZ) was approved, initially for the treatment of trigeminal neuralgia; later, in 1974, it was approved for partial seizures. Ethosuximide has been used since 1958 as a first-choice drug for the treatment of absence seizures without generalized tonic-clonic seizures. Valproate (VPA) was licensed in Europe in 1960 and in the United States in 1978, and now is widely available throughout the world. It became the drug of choice in primary generalized epilepsies and in the mid 1990s was approved for treatment of partial seizures.

These anticonvulsants were the mainstays of seizure treatment until the 1990s, when newer AEDs with good efficacy, fewer toxic effects, better tolerability, and no need for blood level monitoring were developed. A study of live-born infants in Denmark found that exposure to the newer-generation AEDs lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam in the first trimester was not associated with an increased risk in major birth defects. [1]

The new AEDs have been approved in the United States as add-on therapy only, with the exception of topiramate and oxcarbazepine (OXC); lamotrigine (LTG) is approved for conversion to monotherapy. A meta-analysis of 70 randomized clinical trials confirms the clinical impression that efficacy does not significantly differ among AEDs used for refractory partial epilepsy. [2]

Antiepileptic drugs should be used carefully, with consideration of medication interactions and potential side effects. This is particularly important for special populations, such as patients with HIV/AIDS. [3]

For more information, see Epilepsy and Seizures.

Mechanism of Action

It is important to understand the mechanisms of action and the pharmacokinetics of antiepileptic drugs (AEDs) so that these agents can be used effectively in clinical practice, especially in multidrug regimens (see the image below).

Pearls of antiepileptic drug use and management.
Pearls of antiepileptic drug use and management.

Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. The AEDs are designed to modify these processes so as to favor inhibition over excitation and thereby stop or prevent seizure activity (see the image below).

Dynamic target of seizure control in management of epilepsy is achieving balance between factors that influence excitatory postsynaptic potential (EPSP) and those that influence inhibitory postsynaptic potential (IPSP).

The AEDs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action. The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below).

Antiepileptic drugs can be grouped according to th
Antiepileptic drugs can be grouped according to their major mechanism of action. Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action.

[…]

For more Visit site —>  Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers

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[WEB SITE] Small device detects initial signal of epileptic attack and provides effective relief.

Published on August 23, 2016 

The results, from the Laboratory for Organic Electronics at LiU’s Campus Norrköping, have been published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS), with Asst. Prof. Daniel Simon as main author.

According to a recently produced estimate, no less than six percent of the Earth’s population suffers from some type of neurological illness such as epilepsy or Parkinson’s. Some medicines are available, but when these are taken orally or injected into the bloodstream, they also end up where they aren’t needed and may cause serious problems. All medicines have more or less severe side effects, and no fully satisfactory treatment for neurological illnesses is available.

Neurons, or nerve cells, are the cells in the body that both transmit and receive nerve impulses. The small 20×20 µm device developed by the scientists can both capture signals and stop them in the exact area of nerve cells where they arise. No other part of the body needs to be involved.

“Our technology makes it possible to interact with both healthy and sick neurons. We can now start investigating opportunities for finding therapies for neurological illnesses that arise so rapidly and so locally that the patient doesn’t notice them,” says Daniel Simon.

The experiments were conducted in the laboratory on slices of brains from mice. The device consists of a sensor that detects nerve signals, and a small ion pump that doses an exact amount of the neurotransmitter GABA, a substance the body itself uses to inhibit stimuli in the central nervous system.

“The same electrode that registers the activity in the cell can also deliver the transmitter. We call it a bioelectronic ‘neural pixel’, since it imitates the functions of biological neurons,” says Daniel Simon.

“Signalling in biological systems is based on chemical signals in the form of cations, which are passed between transmitters and receptors, which consist of proteins. When a signal is transferred to another cell, the identification of the signal and the triggering of a new one occur within a very small distance – only a few nanometers. In certain cases, it happens at the same point. That’s why being able to combine electronic detection and release in the same electrode is a major advance,” says Professor Magnus Berggren.

The small ion pump, which was developed at the Laboratory for Organic Electronics, attracted a great deal of attention when it´s first application as a therapeutic device was published a year ago. The sensor that captures the nerve signal has subsequently been developed by the LiU researchers’ collaborators at the école Nationale Supérieure des Mines in Gardanne, France. The mouse experiments were performed at Aix-Marseille University. The entire device is manufactured from conductive, biocompatible plastic.

Source: Small device detects initial signal of epileptic attack and provides effective relief

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