Posts Tagged gamma-aminobutyric acid

[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] 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] The New Compounds That Could Treat Depression in 24-Hours

Post image for The New Compounds That Could Treat Depression in 24-HoursCurrent antidepressants take around 3 to 8 weeks to kick in and only help around 50% of people who are depressed.

A new type of antidepressant holds the promise of treating depression quickly, without too many side-effects. Professor Scott Thompson, of the University of Maryland School of Medicine who led the research, said:

“Our results open up a whole new class of potential antidepressant medications.

We have evidence that these compounds can relieve the devastating symptoms of depression in less than one day, and can do so in a way that limits some of the key disadvantages of current approaches.”

Currently used antidepressants, such as Prozac and Lexapro, target levels of the neurotransmitter serotonin.

Unfortunately they are only effective in around half of people with depression. Even amongst people they do help, it can take three to eight weeks for the effects can be felt. For patients who are suicidal, this period can be excruciating.

Also, many now believe that targeting serotonin is not effective (see: Long-Held Belief About Depression Challenged by New Study).

The new compounds focus on another neurotransmitter with the acronym GABA (gamma-aminobutyric acid), instead of serotonin. GABA mainly reduces brain activity in certain key areas related to mood.

The new class of compounds dampen down these inhibitory signals. Theoretically, the result should be to lift mood.

Professor Thompson explained that preliminary tests on animals have been encouraging:

“These compounds produced the most dramatic effects in animal studies that we could have hoped for.

It will now be tremendously exciting to find out whether they produce similar effects in depressed patients.

If these compounds can quickly provide relief of the symptoms of human depression, such as suicidal thinking, it could revolutionize the way patients are treated.”

The study found that the compounds only affected the brains of stressed rats and left unstressed rats unchanged. This may mean that the side-effects of the treatment will be less severe than those seen for current antidepressants.

The study was published in the journal Neuropsychopharmacology (Fischell et al., 2015).

via The New Compounds That Could Treat Depression in 24-Hours.

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