A potential new therapeutic strategy for treating Fragile X syndrome is detailed in a new report appearing in the current issue of Biological Psychiatry, from researchers led by Dr. Lucia Ciranna at University of Catania in Italy.
Fragile X syndrome (FXS), the most common heritable form of autism and intellectual disability, is one of the most exciting areas in brain research at the moment.
A decade ago, Dr. Mark Bear and his colleagues discovered that an animal model for FXS was associated with a distinctive alteration in brain function, enhanced long-term depression, which was mediated by a specific mechanism, enhanced signaling via the metabotropic glutamate receptor 5 (mGluR5). Dr. Bear and his colleagues proceeded to show that blocking mGluR5 showed promise in animal models as the first treatment for FXS. A recent preliminary study of the drug fenobam, an mGluR5 blocker, provided hints of some beneficial effects in adults with FXS.
mGluR5 blockers are likely to be the first examples of several therapeutic mechanisms that will emerge in upcoming years. Now, Ciranna and colleagues have identified another potential therapeutic mechanism for FXS.
Using a mouse model of FXS, they demonstrate that blockade of the serotonin 7 (5-HT7) receptor, like mGluR5 blockade, reduces long-term depression mediated by mGlu receptors. In neuroscience, long-term depression is the term used to describe a reduction or decrease in the effectiveness of neuronal synapses, meaning that the ability of nerve cells to communicate is diminished.
The effect that they detected occurred in the hippocampus, one of the brain structures most crucially involved in learning and memory.
"This result opens new perspectives in the therapy of Fragile X Syndrome, suggesting that selective agonists for 5-HT7 receptors might become useful pharmacological tools," said Ciranna.
This led them to study the effects of LP-211, a new compound with a high affinity and selectivity for 5-HT7 receptors. The data showed that LP-211 behaves as an agonist of 5-HT7 receptors and therefore, may be used as a potential treatment for Fragile X syndrome, although much more work would be necessary before it could be tested in humans.
"This study illustrates a critical issue in the development of new treatments for psychiatric disorders. It is uncommon that all patients with a particular disorder will tolerate or respond to a single treatment. Thus, we need multiple approaches to treatment," commented Dr. John Krystal, Editor of Biological Psychiatry. "Further, this study illustrates how a single insight into the biology of an illness, in this case enhanced mGluR5 signaling, yields multiple novel mechanisms that might be explored to develop novel treatments."
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Mother deer rushed towards the infant distress calls of seals, humans and even bats, suggesting that these mammals share similar emotions
In the forests of eastern Australia, a squadron of social spiders faces off against an army of the world's most dangerous ants in a pitched battle for survival
Contrary to some earlier projections, the world's population will soar through the end of the 21st century thanks largely to sub-Saharan Africa's higher-than-expected birth rates, United Nations and other population experts said on Thursday.
Archaeologists got to the root of an ancient hairstyle when they unearthed a 3,300-year-old body with 70 hair extensions
A major international study finds that killings among chimpanzees result from normal competition, not human interference.
Clownfish travel hundreds of kilometres, but it is the larvae rather than the adults that migrate
U.S. government researchers working with divers and sonar equipment have located the wrecks of what they dubbed "forgotten ghost ships" in waters just outside San Francisco's Golden Gate strait.
"It's spooky," a Clearwater, Fla., fisherman said, comparing the toxic algae bloom to "boiled red Georgia clay"
Physicist Danielle Bassett has been awarded a MacArthur Fellowship based on her work studying the human brain. She talks with Melissa Block about the advances it may lead to.
A team of researchers are using multispectral imaging to uncover hidden text on a 1491 Martellus map, one of the most important maps in history. Lead researcher Chet Van Duzer thinks the discoveries will allow historians and scholars to see just how the map influenced cartography in its time.