Anesthesiologist Paul Garcia and his colleagues are presenting two posters at the Society of Neuroscience meeting this week, whose findings may raise concerns about two non-stimulant drugs Emory sleep specialists have studied for the treatment of hypersomnia: flumazenil and clarithromycin.
For both, the data is in vitro only, so caution is in order and more investigation may be needed.
With flumazenil, Garcia and colleagues found that when neurons are exposed to a low dose for 24 hours, the cells increase expression of some GABA receptor forms.
This could be part of a mechanism for tolerance. I heard some anecdotes describing how flumazenil’s wake-promoting effects wear off over time at the Hypersomnia Foundation conference in July, but it’s not clear how common the phenomenon is.
Flumazenil’s utility in hypersomnia became known after the pioneering experience of Anna Sumner, who has reported being able to use the medicine for years. See this 2013 story in Emory Medicine. Read more
Iâ€™d like to highlight a paper in PLOS One from anesthesiologists Shan Ping Yu and Ling Weiâ€™s group that was published earlier this year. [Sorry for missing it then!] They are investigating potential therapies for stroke, long a frustrating area of clinical research. The â€œclot-bustingâ€ drug tPA remains the only FDA-approved therapy, despite decades of work on potential neuroprotective agents.
Yuâ€™s team takes a different tactic. They seek to bolster the brainâ€™s recovery powers after stroke by mobilizing endogenous progenitor cells. I will call this approach â€œstem cells lite.â€
PTH appears to encourage new neurons in recovery in a mouse model of ischemicÂ stroke. Green = recent cell division, red = neuronal marker
It is similar to that taken by cardiologistÂ Arshed Quyyumi and colleagues with peripheral artery disease: use a growthÂ factorÂ (GM-CSF), which is usually employed for another purpose, to get the bodyâ€™s own regenerative agents to emerge from the bone marrow.
In this case, Yuâ€™s team wasÂ using parathyroid hormone (PTH), which is an FDA-approved treatment for osteoporosis. They administered it, beginning one hour after loss of blood flow, in a mouse model of ischemic stroke. They foundÂ that daily treatment with PTH spurs production of endogenousÂ regenerative factors in the stroke-affected area of the brain. They observed both increased new neuron formation and sensorimotor functional recovery. However, PTH does not pass through the blood-brain barrier and does not change the size of the stroke-affected area, the researchers found.
The conclusion of the paper hints at their next steps:
As this is the first report on this PTH therapy for ischemic stroke for the demonstration of the efficacy and feasibility, PTH treatment was initiated at 1 hr after stroke followed by repeated administrations for 6 days. We expect that even more delayed treatment of PTH, e.g. several hrs after stroke, can be beneficial in promoting chronic angiogenesis and other tissue repair processes. This possibility, however, remains to be further evaluated in a more translational investigation.
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