Itâ€™s not sleep apnea. Itâ€™s not narcolepsy. Hypersomnia is a different kind of sleep disorder. Thereâ€™s even an â€œapples and orangesâ€ 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 â€“ hence the T-shirts.
The story of how sleep took over one young lawyerâ€™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 Sumnerâ€™s, and several questions need answers. Read more
NMDA receptors are saddled with an unwieldy name, but they are some of the most important* signaling molecules in the brain, both for learning and memory and in neurological and psychiatric diseases.
Kasper Hansen, a postdoc from Stephen Traynelis’ lab who is establishing his own at the University of Montana, is lead author on a recent paper in Neuron, which could spur research on NMDA receptors’ pharmacological properties.
The NMDA receptors in the brain are actually mix-and-match assemblies of four subunits, and most of the time in the brain, three different proteins come together to make one receptor, the authors explain. In the laboratory, it has been easier to study simpler, more homogenous, but also more artificial constructs. Hansen and his colleagues developed a way to build replicas of the more complicated NMDA receptors found in the brain and probe their distinct responses to drugs. Read more
Two feature articles in Nature this week on work by Emory scientists.
One is from Virginia Hughes (Phenomena/SFARI/MATTER), delving into Kerry Ressler’s and Brian Dias’ surprising discovery in mice that sensitivity to a smell can be inherited, apparently epigenetically. Coincidentally, Ressler will be giving next week’s Dean’s Distinguished Faculty lecture (March 12, 5:30 pm at the School of Medicine).
Another is from Seattle global health writer Tom Paulson, on immunologist Bali Pulendran and using systems biology to unlock new insights into vaccine design.
This is a continuation of previous posts on individualized treatment for infantile-onset epilepsy, made possible by Emory scientists Stephen Traynelis and Hongjie Yuanâ€™s collaboration with the NIH Undiagnosed Diseases Program. A companion paper containing some clinical details was recently published in Annals of Clinical and Translational Neurology.
Memantine, which was found to be effective for this particular child, is normally used to treat symptoms of Alzheimerâ€™s disease. He has a mutation in a gene encoding a NMDA receptor, an important signaling molecule in the brain, which hyperactivates the receptor. Treatment with memantine reduced his seizure frequency from 11 per week to three per week, and eliminated one type of seizure, myoclonic jerks. It allowed doctors to taper off conventional anticonvulsant drugs, which were having little effect anyway. His cognitive ability has remained unchanged.
The team also discovered that the compound dextromethorphan, found in many over-the-counter cough medicines, was effective in the laboratory in counteracting the effects of a GRIN2A mutation found in another patient. However, these effects were mutually exclusive, because the molecular effects of the mutations are different; memantine helps L812M, while dextromethorphan helps N615K.
Yuan and Traynelis report they have an Fake Oakleys ongoing collaboration with UDP investigators to analyze the effects of mutations in NMDA receptor genes. That means more intriguing case reports are coming, they say.
Tyler Pierson, MD, PhD, lead author of the clinical paper who is now at Cedars-Sinai Medical Center in Los Angeles, and David Adams, MD, PhD, senior staff clinician at NIH, provided some additional information on the patient in the study, shown here in a Q + A format. Read more
This is a continuation of the post from last week on the early-onset epilepsy patient, whom doctors were able to devise an individualized treatment for. The treatment was based on Emory research on the molecular effects of a mutation in the patientâ€™s GRIN2A gene, discovered through whole exome sequencing.*
For this patient, investigators were able to find the Ray Ban Baratas cause for a previously difficult to diagnose case, and then use a medication usually used for Alzheimerâ€™s disease (memantine) to reduce his seizure frequency.
Last week, I posed the question: how often do we move from a disease-causing mutation to tailored treatment? Read more
Peng Jin and collaborators led by Da-Hua Chen from the Institute of Zoology, Chinese Academy of Sciences have a new paper in Stem Cell Reports. They describe a souped-up method for producing iPS cells (induced pluripotent stem cells).
Production of iPS cells in the laboratory is becoming more widespread. Many investigators, including those at Emory, are using the technology to establish â€œdisease in a dishâ€ models and derive iPS cells from patient donations, turning them into tools for personalized medicine research.
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 itâ€™s quite rare.
How rare this is, Iâ€™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 Healthâ€™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 Alzheimerâ€™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.]
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.Â 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.Â 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).Â Kerry Ressler (fear learning/PTSD) was supposed to be last week but that was derailed by ice. So Ressler will speak Â on May 21, according to organizer Victor Faundez, who chose Picasso’s Guernica as the visual theme.
The word “chaperone” refers to an adult who keeps teenagers from acting up at a dance or overnight trip. It also describes a type of protein that can guard the brain against its own troublemakers: misfolded proteins that are involved in several neurodegenerative diseases.
Researchers at Emory University School of Medicine led by Shihua Li, MD, and Xiao-Jiang Li, MD, PhDÂ have demonstrated that as animals age, their brains are more vulnerable to misfolded proteins, partly because of a decline in chaperone activity.
The researchers were studying a model of spinocerebellar ataxia, but the findings have implications for understanding other diseases, such as Alzheimer’s, Parkinson’s and Ray Ban outlet Huntington’s. They also identified targets for potential therapies: bolstering levels of either a particular chaperone or a growth factor in brain cells can protect against the toxic effects of misfolded proteins.
The results were published recently in the journalÂ Neuron. Read more
This intriguing research has received plenty of attention, Â 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.Â 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: