Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Emory researchers see investigating 3q29 deletion as a way of unraveling schizophrenia’s biological and genetic Read more

B cells off the rails early in lupus

Emory scientists could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously Read more

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

fragile X

Fragile X clinical trial update

A recent issue of Emory Health magazine had an article describing the progress of clinical trials for fragile X syndrome, the most common inherited cause of intellectual disability. The article included interviews with the parents of a boy, Samuel McKinnon, who is participating in one of the phase III clinical trials here at Emory.

Last week, results for the phase II study for the same medication were published in Science Translational Medicine. The drug, called STX209 or arbaclofen, is one of the first designed to treat the molecular changes in the brain caused by fragile X syndrome. STX209 shows some promise in its ability to reduce social withdrawal, a key symptom of fragile X syndrome.

In one case, a boy was able to attend his birthday party for the first time in his life. In the past, he had been too shy and couldn’t tolerate hearing people sing Happy Birthday to You, the study’s lead author Elizabeth Berry-Kravis, MD, PhD from Rush University, told USA Today.

These results have generated excitement among autism researchers and specialists, because a fraction of individuals with fragile X mutations have autism and the same drug strategy may be able to address deficits in other forms of autism.

Some caveats:
1. Autism and fragile X are not the same thing.
2. This was a phase II study, the phase III results are yet to come.
3. The study authors are up front about saying that the “primary endpoint” (irritability) showed no difference between drug and placebo.

A team led by Emory genetics chair Steve Warren identified the gene responsible for fragile X in 1991, and Emory scientists have been important players in figuring out its effects on the brain.

Warren and colleague Mika Kinoshita are co-authors on a companion paper in STM on treatment of fragile X mice. A thoughtful review piece in the same issue of STM lays out current issues in developing therapies for “childhood disorders of the synapse.”

Posted on by Quinn Eastman in Neuro Leave a comment

Fragile X protein: one toggle switch, many circuits

The fragile X protein — missing in the most common inherited form of intellectual disability — plays a central role in neurons and how they respond to external signals. Cell biologist Gary Bassell and his colleagues have been examining how the fragile X protein (FMRP) acts as a “toggle switch.”

Gary Bassell, PhD

FMRP controls the activity of several genes by holding on to the RNAs those genes encode. When neurons get an electrochemical signal from the outside, FMRP releases the RNAs, allowing the RNAs to be made into protein, and facilitating changes in the neurons linked to learning and memory.

The Bassell lab’s new paper in Journal of Neuroscience reveals the role of another player in this process. The first author is postdoctoral fellow Vijay Nalavadi.

The researchers show that neurons modify FMRP with ubiquitin, the cellular equivalent of a tag for trash pickup, after receiving an external signal. In general, cells attach ubiquitin to proteins so that the proteins get eaten up by the proteasome, the cellular trash disposal bin. Here, neurons are temporarily getting rid of FMRP, prolonging the effects of the external signal.

Posted on by Quinn Eastman in Neuro Leave a comment