Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

Anti-inflammatory approach suppresses cancer metastasis in animal models

An anti-inflammatory drug called ketorolac, given before surgery, can promote long-term survival in animal models of cancer metastasis, a team of scientists has found. The research suggests that flanking chemotherapy with ketorolac or similar drugs -- an approach that is distinct from previous anti-inflammatory cancer prevention efforts -- can unleash anti-tumor immunity. The findings, published in Journal of Clinical Investigation, also provide a mechanistic explanation for the anti-metastatic effects of ketorolac, previously observed in human Read more

I3 Venture awards info

Emory is full of fledgling biomedical proto-companies. Some of them are actual corporations with employees, while others are ideas that need a push to get them to that point. Along with the companies highlighted by the Emory Biotech Consulting Club, Dean Sukhatme’s recent announcement of five I3 Venture research awards gives more examples of early stage research projects with commercial potential. This is the third round of the I3 awards; the first two were Wow! Read more

Bmal1

Circadian rhythms go both ways: in and from retina

In case you missed it, the 2017 Nobel Prize in Medicine marked the arrival of the flourishing circadian rhythm field. Emory Eye Center’s Mike Iuvone teamed up with Gianluca Tosini at Morehouse School of Medicine to probe how a genetic disruption of circadian rhythms affects the retina in mice.

Removal of the Bmal1 gene – an essential part of the body’s internal clock — from the retina in mice was known to disrupt the electrical response to light in the eye. The “master clock” in the body is set by the suprachiasmatic nucleus, part of the hypothalamus, which receives signals from the retina. Peripheral tissues, such as the liver and muscles, have their own clocks. The retina is not so peripheral to circadian rhythm, but its cellular clocks are important too.

What the new paper in PNAS shows is that removal of Bmal1 from the retina accelerates the deterioration of vision that comes with aging, but it also shows developmental effects – see below.

You might think: “OK, the mice have disrupted circadian rhythms for their whole lives, so that’s why their retinas are messed up.” But the Emory/Morehouse experimenters removed the Bmal1 gene from the retina only.

P. Michael Iuvone, PhD, director of vision research at Emory Eye Center

The authors write: “BMAL1 appears to play important roles in both cone development and cone viability during aging… Cones are known to be among the cells with highest metabolism within the body and therefore, alteration of metabolic processes within these cells is likely to affect their health status and viability.”

More from the official news release:

…Bmal1 removal significantly affects visual information processing and reduces the thickness of inner retinal layers. The absence of Bmal1 also affected visual acuity and contrast sensitivity. Another important finding was a significant age-related decrease in the number of cone photoreceptors (outer segments and nuclei) in mice lacking Bmal1, which suggests that these cells are directly affected by Bmal1 removal.

“When we genetically disrupted the circadian clocks in the retinas of mice, we found accelerated age-related cone photoreceptor death, similar to that in age-related macular degeneration in humans,” Iuvone says. “This loss of photoreceptor cones affects retinal responses to bright light.

“We also noted developmental effects in young mice,” Iuvone continues, “including abnormalities in rod bipolar cells that affected dim light responses. These findings have potential implications for pregnant shift workers and other women with sleep and circadian disorders, whose offspring might develop visual problems due to their mother’s circadian disruption.”

 

 

Posted on by Quinn Eastman in Neuro Leave a comment