The investigation follows up on research by molecular neuroscientist Fang Liu, Ph.D., in which Liu developed a protein peptide that provided a highly targeted approach to treating depression that she hopes will have minimal side effects.
However, the peptide had to be injected into the brain. Taken orally, it would not cross the blood-brain barrier in sufficient concentration.
The new study introduces the use of a nasal spray system to deliver the peptide to the right part of the brain.
“Clinically, we needed to find a non-invasive, convenient method to deliver this peptide treatment,” said Liu, senior scientist at the Centre for Addiction and Mental Health.
With the support of a Proof of Principle grant from the Canadian Institutes of Health Research, Liu’s team was able to further explore novel delivery methods.
The nasal delivery system, developed by U.S. company Impel NeuroPharma, was shown to deliver the peptide to the right part of the brain. It also relieved depression-like symptoms in animals.
The study is published online in the journal Neuropsychopharmacology.
“This study marks the first time a peptide treatment has been delivered through nasal passageways to treat depression,” said Liu, professor in the University of Toronto’s Department of Psychiatry.
“The peptide treatment interferes with the binding of two dopamine receptors — the D1 and D2 receptor complex. Liu’s team had found that this binding was higher in the brains of people with major depression. Disrupting the binding led to the antidepressant effects,” she said.
The peptide is an entirely new approach to treating depression, which has previously relied on medications that primarily block serotonin or norepinephrine transporters.
Depression, the most common form of mental illness, is one of the leading causes of disability globally. More than 50 percent of people living with depression do not respond to first-line drug treatment.
“This research brings us one step closer to clinical trials,” Liu said.
In ongoing lab research, her team is experimenting to determine if they can make the peptide break down more slowly, and travel more quickly in the brain, to improve its antidepressant effects.