A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose.

The novel therapeutic targets brain receptors responsible for learning and memory — a very different approach from existing antidepressants. The new drug and others like it also could be helpful in treating other neurological conditions, including schizophrenia, bipolar disorder, anxiety and Alzheimer’s disease.

The results of the phase IIa clinical trial were presented today (Dec. 6) at the 51st Annual Meeting of the American College of Neuropsychopharmacology in Hollywood, Fla.

Also this week a paper reporting some of the background scientific research that provided the foundation for the clinical development of GLYX-13 was published by the journal Neuropsychopharmacology.

The compound, called GLYX-13, is the result of more than two decades of work by Joseph Moskal, research professor of biomedical engineering at Northwestern’s McCormick School of Engineering and Applied Science and director of the University’s Falk Center for Molecular Therapeutics.

“Our study showed that this compound is capable of eliciting a robust and rapid antidepressant effect without the typical side effects seen with other drugs that also modulate the NMDA receptor,” said Moskal, who is founder and chief scientific officer of the Evanston-based biotechnology company Naurex Inc., which conducted the clinical study.

GLYX-13 works by modulating the NMDA (N-methyl-D-aspartate) receptor in the brain, as do current NMDA receptor antagonists such as ketamine, but GLYX-13 does not have their serious and limiting side effects, such as hallucinations and schizophrenia-like effects. (An antagonist is a substance that inhibits the physiological action of another.)

Moskal and his team have figured out a new way to target the NMDA receptors that maintains the positive antidepressant properties while eliminating the negative side effects.

In clinical trials administered at 12 sites across the country, a single dose of GLYX-13 resulted in significant reductions in depression symptoms among subjects who had shown little improvement with previous drugs. (Subjects had failed treatment with one or more antidepressant agents.)

The positive effects of GLYX-13 were evident within 24 hours and lasted an average of seven days. The effect size, a measure of the magnitude of the drug’s antidepressant efficacy, at both these times after a single dose was nearly double the effect size seen with most other antidepressant drugs after four to six weeks of repeated dosing.

Side effects of GLYX-13 were mild to moderate and were consistent with those observed in subjects receiving a placebo.

GLYX-13 is a four-amino acid peptide that modulates one of a large family of glutamate receptors, the NMDA (N-methyl-D-aspartate) receptor, in the brain. NMDA receptors play a key role in regulating synaptic plasticity — the quality of the connection between neurons — and thus are important in regulating learning and memory functions.

GLYX-13 is administered intravenously. Moskal said Naurex also is working on an oral drug with similar properties and potential.

Moskal hopes that these positive GLYX-13 results and the research efforts of his team and colleagues will help shepherd in more research and grant support for studying the role of the glutamate-mediated processes in neuropsychiatric disorders.

“While the results we are seeing with GLYX-13 are very encouraging, I believe the most important research is yet to come,” Moskal said. “We have only scratched the surface of the therapeutic potential of the glutamatergic system.”

GLYX-13 currently is undergoing a phase IIb clinical trial at 20 sites across the United States. This trial is evaluating repeated doses of the drug.

The Neuropsychopharmacology paper is titled “GLYX-13, an NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects.”

The research was supported by grants from the Ralph and Marian Falk Medical Research Trust, the Hope for Depression Research Foundation and the National Institutes of Health (grants MH094835, NS044421 and DA01442).

Northwestern University has exclusively licensed the intellectual property rights related to the therapeutics developed by Joseph Moskal while at the University to Naurex Inc. Northwestern also has a small equity position in Naurex.

Northwestern University

Researchers at the University of Edinburgh Business School found that more Facebook friends means more stress.

A large number of friends on Facebook may appear impressive but, according to a new report, the more social circles a person is linked to online the more likely social media will be a source of stress.

A report from the University of Edinburgh Business School has found that the more groups of people in someone’s Facebook friends, the greater potential to cause offence. In particular, adding employers or parents resulted in the greatest increase in anxiety.

Stress arises when a user presents a version of themself on Facebook that is unacceptable to some of their online ‘friends’, such as posts displaying behaviour such as swearing, recklessness, drinking and smoking.

As older people join the site, this has become an increasing problem as their expectations may
be very different from those of younger users.

Some 55 per cent of parents follow their children on Facebook. Likewise, more than half of employers claim not to have hired someone based on their Facebook page. Researchers found that on average people are Facebook friends with seven different social circles. The most common group was friends known offline (97 per cent added them as friends online), followed by extended family (81 per cent), siblings (80 per cent), friends of friends (69 per cent), and colleagues (65 per cent).

The report also discovered that more people are Facebook friends with their former partners than with their current relationship partner. Only 56 per cent of users were friends with their boyfriend, girlfriend or spouse online, compared with 64 per cent of exes.

The report surveyed more than 300 people on Facebook, mostly students, with an average age
of 21. It also discovered that only one third use the listing privacy setting on their Facebook profile, which can be used to control the information seen by different types of friends.

Ben Marder, author of the report and early career fellow in marketing at the Business School, said: “Facebook used to be like a great party for all your friends where you can dance, drink and flirt. But now with your Mum, Dad and boss there the party becomes an anxious event full
of potential social landmines.

Source:University of Edinburgh Business School