Cancer research: souping up adoptive cell therapy

Several current clinical trials are testing CpG or related TLR9 agonists, but mostly in the context of delivering them as in vivo adjuvants. This is Read more

Report on first Omicron case detected in GA

The first Omicron case detected in Georgia probably became infected during a visit to Cape Town, South Read more

Neuro

True personalized medicine: from mutation to treatment

Stephen Traynelis and Hongjie Yuan

Stephen Traynelis, PhD and Hongjie Yuan, MD, PhD

How often can doctors go from encountering a patient with a mysterious disease, to finding a mutation in a gene that causes that disease, to developing a treatment crafted for that mutation?

This is true personalized molecular medicine, but it’s quite rare.

How rare this is, I’d like to explore more, but first I should explain the basics.

At Emory, Stephen Traynelis and Hongjie Yuan have been working with Tyler Pierson, David Adams, William Gahl, Cornelius Boerkoel and doctors at the National Institutes of Health’s Undiagnosed Diseases Program (UDP) to investigate the effects of mutations in the GRIN2A gene.

Their report on the molecular effects of one such mutation, which caused early-onset epilepsy and intractable seizures in a UDP patient, was recently published in Nature Communications.

With that information in hand, UDP investigators were able to repurpose an Alzheimer’s medication as an anticonvulsant that was effective in reducing seizure frequency in that patient. [The details on that are still unpublished but coming soon.]

Read more

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Local events: complex neuro diseases, DNA repair

Just a note for Atlanta-area readers about two interesting lecture series.

One is the Suddath Symposium, a two-day event today and Friday at Georgia Tech focusing on DNA repair in human disease. This is an area that Emory is strong in: Gray Crouse, Paul Doetsch, Willian Dynan and Gang Bao are speaking (all on Friday).

Another is a series of talks from Emory investigators on http://www.raybani.com/ complex neurological diseases, being put on by the Department of Cell Biology. Four, one a week (originally), all on Wednesdays at 4 pm in Whitehead 400.

Yesterday: Peter Wenner (homeostatic mechanisms/scaling). Feb. 26: Shannon Gourley (stress hormones/distorted decision-making/depression). March 5: Andrew Escayg (sodium channels/inherited epilepsy). Kerry Ressler (fear learning/PTSD) was supposed to be last week but that was derailed by ice. So Ressler will speak  on May 21, according to organizer Victor Faundez, who chose Picasso’s Guernica as the visual theme.

 

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment

Talkin’ about epigenetics

This intriguing research has received plenty of attention,  both when it was presented at the Society of Neuroscience meeting in the fall and then when the results were published in Nature Neuroscience.

The short summary is: researchers at Yerkes National Primate Research Center found that when a mouse learns to become afraid of a certain odor, his or her pups will be more Gafas Ray Ban Baratas sensitive to that odor, even though the pups have never encountered it. Both the parent mouse and pups have more space in the smell-processing part of their brains, called the olfactory bulb, devoted to the odor to which they are sensitive.

[Note: a feature on a similar phenomenon, transgenerational inheritance of the effects of chemical exposure, appeared in Science this week]

Somehow information about the parent’s experiences is being inherited. But how? Brian Dias and Kerry Ressler are now pursuing followup experiments to firmly establish what’s going on. They discuss their research in this video:

 

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Eyes on dopamine

Dopamine-restoring drugs already used to treat Parkinson’s disease may also be beneficial for the treatment of diabetic retinopathy, a leading cause of blindness in adults, researchers have discovered. The results were published recently in Journal of Neuroscience.

Diabetic retinopathy affects more than a quarter of adults with diabetes and threatens the vision of more than 600,000 people in the United States. Doctors had previously thought most of the impairment of vision in diabetic retinopathy came from damage to the blood vessels induced by high blood sugar, but had known that dopamine, a vital neurotransmitter in the brain, was also important in the retina.

“There was some evidence already that dopamine levels were reduced in diabetic retinopathy, but what’s new here is: we can restore dopamine levels and improve visual Ray Ban outlet function in an animal model of diabetes,” says Machelle Pardue, PhD, associate professor of ophthalmology at Emory University School of Medicine and research career scientist at the Atlanta VA Medical Center. Read more

Posted on by Quinn Eastman in Neuro 1 Comment

Estrogen receptor gene guides bird behavior

Please head over to our sister blog eScienceCommons to learn about how two types of white-throated sparrow have differences in behavior, which are driven by a chromosomal alteration. Scientists at Emory showed that changes in the estrogen receptor gene are responsible for the behavior differences.

White-striped birds tend to be http://www.magliettedacalcioit.com more aggressive and less parental than the tan-striped birds, you will learn. Hey, that sounds sort of like prairie voles and meadow voles.

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Hypoxia is bad, except when it’s good

Randy Trumbower and his colleagues in Emory’s Department of Rehabilitation Medicine recently published a study showing that “daily intermittent hypoxia,” combined with walking exercise, can help patients with incomplete spinal cord injury walk for longer times. What is it about being deprived of oxygen for short periods that has a positive effect?

This research was puzzling at first (at least to your correspondent) because “daily intermittent hypoxia” is a good description of the gasping and snorting interruptions of sleep apnea.

Sleep apnea is a very common condition that increases the risk of high blood pressure, diabetes, heart attack and stroke. On the other side of the coin, many endurance athletes have been harnessing the body’s ability to adapt to low oxygen levels — so-called altitude training — to increase their performance for years.

So we have an apparent clash: hypoxia is bad, except when it’s good. Looking closely, there are some critical differences between sleep apnea and therapeutic hypoxia. The dose makes the poison, right? Read more

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The classic epilepsy surgery case

The epilepsy patient Henry Molaison, known for most of the 20th century as H.M., is one of the most famous in neuroscience. His case played an important role in telling scientists about structures of the brain that are important for forming short-term and long-term memories.

To control H.M.’s epilepsy, neurosurgeon William Scoville http://www.raybandasoleit.com/ removed much of the hippocampi, amygdalae and nearby regions on both sides of his brain. After the surgery, H.M. suffered from severe anterograde amnesia, meaning that he could not commit new events to explicit memory. However, other forms of his memory were intact, such as short-term working memory and motor skills.Henry_Gustav_1

This classic case helps us understand the advances that neurosurgeons at Emory are achieving today. The surgeries now used to treat some medication-resistant forms of epilepsy are similar to what was performed on H.M., although they are considerably less drastic. Usually tissue on only one side of the brain is removed. Still, there can be cognitive side effects: loss of visual or verbal memory abilities, and deficiencies in the ability to name or recognize objects, places or people.

Neurosurgeon Robert Gross has been a pioneer in testing a more precise procedure, selective laser amygdalohippocampotomy (SLAH), which appears to control seizures while having less severe side effects. Neuropsychologist Daniel Drane reported at the recent American Epilepsy Society meeting on outcomes from a series of SLAH surgeries performed at Emory.

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Alzheimer’s drug discovery: looking under the right ROCK

Developing drugs that can change the progression of Alzheimer’s disease is a huge challenge. In the last few years, more than one pharmaceutical firm have abandoned clinical programs in Alzheimer’s that once looked promising. Still, Emory and Scripps scientists have found an approach that deserves a second look and more investigation.

One straightforward drug strategy against Alzheimer’s is to turn down the brain’s production of beta-amyloid, the key component of the disease’s characteristic plaques. A toxic fragment of a protein found in healthy brains, beta-amyloid accumulates in the brains of people affected by the disease.

The enzyme that determines how much beta-amyloid brain cells generate is called BACE (beta-secretase or beta-site APP cleaving enzyme). Yet finding drugs that inhibit that elusive enzyme has been far from straightforward.

Now researchers  have identified a way to shut down production of beta-amyloid by diverting BACE to a different part of the cell and inhibiting its activity. The results were published this week in Journal of Neuroscience. Read more

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A discriminative stimulus

You may remember Highlights magazine from when you were a kid (or parent). Highlights has a feature where readers have to spot the differences between two similar pictures.

NEDA

Dopamine gets a lot of press, and cocaine addiction research has generally focused more on dopamine. (What is “the molecule behind all our most sinful behaviors and secret cravings?”) Norepinephrine is usually described more prosaically, as a hormone related to attention, stress and blood pressure regulation. Lowering norepinephrine levels does not stop animals from giving themselves a steady stream of cocaine, but it does inhibit their tendency to try to get it after a break or exposure to relapse triggers.

What is the difference between these two important brain communication chemicals, dopamine and norepinephrine? Look closely.

The answer is: just one oxygen atom. But it’s enough to mean http://www.magliettedacalcioit.com that the two neurotransmitters use different receptors and dominate different groups of neurons in the brain.

An area of medicine where that subtle difference is crucial is drug abuse. Geneticist David Weinshenker is an expert on the enzyme that converts dopamine into norepinephrine: dopamine beta-hydroxylase or DBH. He and his lab have been exploring whether medications that inhibit DBH could be used to help treat cocaine addiction. Read more

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Blood pressure meds + PTSD

The connection between stress and blood pressure seems like common sense. Of course experiencing stress — like a narrow miss in morning traffic or dealing with a stubborn, whiny child — raises someone’s blood pressure.

Try reversing the cause-and-effect relationship: not from brain to body, but instead from body to brain. Could medication for controlling blood pressure moderate the effects of severe stress, and thus aid in controlling PTSD symptoms or in preventing the development of PTSD after trauma?

That was the intriguing implication arising from a 2012 paper from Grady Trauma Project investigators led by psychiatrist Kerry Ressler (lab at Yerkes, supported by HHMI).

They had found that traumatized civilians who take either of two classes of common blood pressure medications tend to have less severe post-traumatic stress symptoms. In particular, individuals taking ACE inhibitors (angiotensin converting enzyme) or ARBs (angiotensin receptor blockers) tended to have lower levels of hyperarousal and intrusive thoughts, and this effect was not observed with other blood pressure medications.

This was one of those observational findings that needs to be tested in an active way: “OK, people who are already taking more X experience less severe symptoms. But can we actually use X as an intervention?”

In mice, it seems to work. Read more

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