Gene editing reverses Huntington's in mouse model

This is a concrete example, not yet clinical, of what can be done with CRISPR/Cas9 gene Read more

Urine tests for prostate cancer could reduce biopsies

Urine RNA tests could reduce the number of biopsies by giving a preview of a cancer's aggressiveness. Featuring Martin Sanda and Carlos Read more

Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

Department of Neurology

Mitochondrial blindness — Newman’s Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy.

The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials (REVERSE and RESCUE) are ongoing.

Despite all the progress, there are still several puzzles connected with mitochondrial diseases affecting vision and particularly Leber’s, the first human disease linked to mitochondrial DNA mutations by Douglas Wallace at Emory in the 1980s.

Newman called Leber’s an “ideal laboratory” for studying mitochondrial diseases of vision, because deterioration of vision in Leber’s tends to happen to one eye first, presenting a window of opportunity to deliver treatment to the other eye. Read more

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Enhanced verbal abilities in the congenitally blind

A recent paper in Experimental Brain Research from Emory neuroscientist Krish Sathian and colleagues demonstrates that congenitally blind study participants displayed superior verbal, but not spatial abilities, when compared to their sighted counterparts. This may reflect both greater reliance on verbal information, and the recruitment of the visual cortex for verbal tasks.

Sathian’s team has also been investigating, through brain imaging studies, whether the visual cortex is involved in the processing of metaphors (2016 SFN abstract) in the congenitally blind. They previously showed that blind study participants were better at identifying rotated objects by touch. Read more

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How “twist my arm” engages the brain

Listening to metaphors involving arms or legs loops in a region of the brain responsible for visual perception of those body parts, scientists have discovered.

The finding, recently published in Brain & Language, is another example of how neuroscience studies are providing evidence for “grounded cognition” – the idea that comprehension of abstract concepts in the brain is built upon concrete experiences, a proposal whose history extends back millennia to Aristotle.

The EBA was shown in 2001 to respond selectively to images of the human body by Nancy Kanwisher and colleagues.

When study participants heard sentences that included phrases such as “shoulder responsibility,” “foot the bill” or “twist my arm”, they tended to engage a region of the brain called the left extrastriate body area or EBA.

The same level of activation was not seen when participants heard literal sentences containing phrases with a similar meaning, such as “take responsibility” or “pay the bill.”  The study included 12 right-handed, English-speaking people, and blood flow in their brains was monitored by functional MRI (magnetic resonance imaging).

“The EBA is part of the extrastriate visual cortex, and it was known to be involved in identifying body parts,” says senior author Krish Sathian, MD, PhD, professor of neurology, rehabilitation medicine, and psychology at Emory University.  “We found that the metaphor selectivity of the EBA matches its visual selectivity.” Read more

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Sensory connections spill over in synesthesia

Neuroscientists at Emory University have found that people who experience a mixing of the senses, known as synesthesia, are more sensitive to associations everyone has between the sounds of words and visual shapes. The results are published in the European Journal of Neuroscience.

Synesthesia is a stable trait, and estimated to be present in 1 to 4 percent of people. It can be inherited, although the precise genes have not been identified. One of the most common forms of synesthesia is when people involuntarily see particular colors in connection with letters, numbers or sounds.

Many artists and composers have described their experiences with synesthesia. Children with synesthesia say sometimes that it is distracting when they are trying to read. Thus, understanding the origins of synesthesia may help people with dyslexia or other learning differences, or people who have lost their sight or hearing and are trying to engage in sensory substitution for rehabilitation.

Researchers led by neurologist Krish Sathian, MD, PhD, recruited 17 people with synesthesia, and asked them to take a form of the IAT (implicit association test). Known for its use probing social attitudes such as racial prejudice, the IAT can also assess “cross-modal correspondences.”

An example of a cross-modal correspondence is that we describe musical notes as being “high” or “low” – words that also signify relative positions in space. Another is that we think of some sounds such as “m” and “l” as soft, and are more likely to associate them with rounded shapes. Similarly, we connect hard sounds such as “k” and “t” with angular shapes.

“There’s been a debate about synesthesia,” Sathian says. “Are the associations synesthetes have just extreme versions of cross-modal correspondences that other people have, or are they qualitatively different?”

Sathian and his colleagues found that people with synesthesia were more sensitive to correspondences between the sounds of pseudowords — words without meaning in English — and rounded or angular shapes. Read more

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The secrets of a new Alzheimer’s secretase

The title of Keqiang Ye’s recent Nature Communications paper contains a provocative name for an enzyme: delta-secretase.

Just from its name, one can tell that a secretase is involved in secreting something. In this case, that something is beta-amyloid, the toxic protein fragment that tends to accumulate in the brains of people with Alzheimer’s disease.

Aficionados of Alzheimer’s research may be familiar with other secretases. Gamma-secretase was the target of some once-promising drugs that failed in clinical trials, partly because they also inhibit Notch signaling, important for development and differentiation in several tissues. Now beta-secretase inhibitors are entering Alzheimer’s clinical trials, with similar concerns about side effects.

Many Alzheimer’s researchers have studied gamma- and beta-secretases, but a review of the literature reveals that so far, only Ye and his colleagues have used the term delta-secretase.

This enzyme previously was called AEP, for asparagine endopeptidase. AEP appears to increase activity in the brain with aging and cleaves APP (amyloid precursor protein) in a way that makes it easier for the real bad guy, beta-secretase, to produce bad beta-amyloid.*At Alzforum, Jessica Shugart describes the enzyme this way:

Like a doting mother, AEP cuts APP into bite-sized portions for toddler BACE1 [beta-secretase] to chew on, facilitating an increase in beta-amyloid production. Read more

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The buzz of consciousness and how seizures disrupt it

These days, it sounds a bit old-fashioned to ask the question: “Where is consciousness located in the brain?” The prevailing thinking is that consciousness lives in the network, rather than in one particular place. Still, neuroscientists sometimes get an intriguing glimpse of a critical link in the network.

A recent paper in the journal Epilepsy & Behavior describes an epilepsy patient who had electrodes implanted within her brain at Emory University Hospital, because neurologists wanted to understand where her seizures were coming from and plan possible surgery. Medication had not controlled her seizures and previous surgery elsewhere had not either.

ElectrodesSmaller

MRI showing electrode placement. Yellow outline indicates the location of the caudate and thalamus. Image from Leeman-Markowsi et al, Epilepsy & Behavior (2015).

During intracranial EEG monitoring, implanted electrodes detected a pattern of signals coming from one part of the thalamus, a central region of the brain. The pattern was present when the patient was conscious, and then stopped as soon as seizure activity made her lose awareness.

The pattern of signals had a characteristic frequency – around 35 times per second – so it helps to think of the signal as an auditory tone. Lead author Beth Leeman-Markowski, director of EUH’s Epilepsy Monitoring Unit at the time when the patient was evaluated, describes the signal as a “buzz.”

“That buzz has something to do with maintenance of consciousness,” she says. Read more

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Hypersomnia update: clarithromycin study

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From Emory Medicine, Spring 2013

A small clinical study of clarithromycin for the sleep disorder hypersomnia shows that the antibiotic can combat patients’ subjective experience of sleepiness, but it does not seem to improve reaction time measured in a video-game-type vigilance task.

The effects of clarithromycin in hypersomnia were first observed by Emory doctors when an early patient (Anna Sumner, whose story is told in this Emory Medicine article) unexpectedly experienced sleeplessness when taking it for a respiratory infection.

The results of the study were published online by Annals of Neurology on June 10.

Lynn Marie Trotti, MD, David Rye, MD, PhD and colleagues from the Department of Neurology and Emory Sleep Center conducted the study, which involved 23 patients.

Advantages of clarithromycin:

  1. It’s inexpensive and widely available.
  2. It’s an option for people dealing with hypersomnia for whom other medications, such as modafinil, are not helpful or tolerable.
  3. It represents an alternative to flumazenil, the benzodiazepine antidote that has been shown to help some hypersomnia patients. Flumazenil used to be very scarce, and shortages occur (Hypersomnia Foundation/American Society of Health System Pharmacists).

Disadvantages of clarithromycin:

  1. It’s an antibiotic, so it probably changes intestinal bacteria.
  2. Chronic use could promote the growth of antibiotic-resistant bacteria.
  3. Most patients reported an altered sense of taste or smell. Some describe this as a metallic mouth sensation.

Read more

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Clot dissolver tPA’s tardy twin could aid in stroke recovery

Emory researchers led by neurologist Manuel Yepes, MD have identified a protein released by neurons while the brain is recovering from a stroke. The results were published online today in Journal of Neuroscience.

The protein, called urokinase-type plasminogen activator or uPA, has been approved by the FDA to dissolve blood clots in the lungs. It has been tested in clinical trials in some countries as a treatment for acute stroke.

The Emory team’s findings suggest that in stroke, uPA’s benefits may extend beyond the time when doctors’ principal goal is dissolving the blood clot that is depriving the brain of blood.
Instead, uPA appears to help brain cells recover from the injuries induced by loss of blood flow. Treating mice with uPA after an experimental stroke can improve their recovery of motor function, the researchers found.

Read more

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Hypersomnia update: beyond subject one

It’s not sleep apnea. It’s not narcolepsy. Hypersomnia is a different kind of sleep disorder. There’s even an “apples and oranges” T-shirt (see below) that makes that point.

This weekend, your correspondent attended a patient-organized Living with Hypersomnia conference. One of the main purposes of the conference was to update sufferers and supporters on the state of research at Emory and elsewhere, but there was also a lot of community building — hence the T-shirts.

The story of how sleep took over one young lawyer’s life, and how her life was then transformed by flumazenil, a scarce antidote to sleeping pills she was not taking, has received plenty of attention.

Now an increasing number of people are emerging who have a condition similar to Anna Sumner’s, and several questions need answers. Read more

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