Effect size within 24 hours after a single dose was nearly double the effect size seen with most other antidepressant drugs after four to six weeks of repeated dosing.
A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested in a 12-site phase IIa trial 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. (A 20-site phase IIb trial now underway is studying the effect of repeated doses.)
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 compound, called GLYX-13, is the result of more than two decades of work by Joseph Moskal, PhD, research professor of biomedical engineering at Northwestern. On Dec 3, the journal Neuropsychopharmacology published a paper describing some of the research underlying the clinical development of GLYX-13. And on Dec 6 Prof Moskal presented the results of the recent trial to members of the American College of Neuropsychopharmacology at their annual meeting in Hollywood, FL.
“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,” says Dr. Moskal, who is founder and chief scientific officer of the Evanston, IL-based biotechnology company Naurex Inc., which conducted the clinical study. (Northwestern has granted to Naurex exclusive licensing of the intellectual property rights related to the therapeutics Dr. Moskal developed while at the University, and has a small equity position in Naurex.)
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.)
Dr. 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 currently administered intravenously, but Naurex is now working on an oral drug with similar properties and potential, Dr. Moskal says.
Further, he says, it is his hope 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,” he adds. “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.
Source: Based on Northwestern University press release by Megan Fellman with contributions by Sarah Ostman, Dec 6, 2012