Researchers use a molecule from the HI virus to introduce an antidepressant protein directly into nerve cells. The therapeutic effect in the mouse model is significantly faster and stronger than with previous drugs.
Antidepressants are the most commonly used psychotropic drugs. However, they often improve the symptoms only after weeks or months, have strong side effects and do not work at all for many sufferers. Now, scientists at Freiburg University Hospital are presenting a new therapeutic approach in the mouse model that could largely solve this problem: They coupled the therapeutically active signal protein Homer1a with a smuggler molecule that also allows the HI virus to enter the cells. In this way, the active ingredient enters the nerve cell and can intervene directly in the cell’s signaling pathways.
“The active ingredient exerts its antidepressant effect without detours and thus significantly faster and more strongly than classic antidepressants,” says study leader Dr. Tsvetan Serchov, research group leader in the Department of Stereotactic and Functional Neurosurgery at the Department of Neurosurgery at Freiburg University Medical Center. The study appeared in the prestigious journal Neuron on August 13, 2019.
Therapeutic approach from the 1980s could take on new significance
The researchers used a process that has been known since the late 1980s but has rarely been used for therapeutic purposes. They linked a tiny protein from the HI virus to the protein Homer1a, which is important for depression therapy. The HIV protein can easily penetrate the cell membrane due to its physicochemical properties. In the process, it transports the therapeutically active Homer protein through the blood-brain barrier and into the cell.
After the scientists put the double molecule into the mice’s blood, it took only about an hour for the antidepressant effect to kick in. In recent years, the Freiburg researchers had identified the protein Homer1a as an important cellular mediator in the therapy of depression. “We were able to show in previous studies that not only drugs, but even the antidepressant effect of sleep deprivation leads to activation of Homer proteins,” Serchov says.
In the current study, which was conducted in close collaboration with physicians and scientists from the Department of Psychiatry and Psychotherapy at Freiburg University Hospital, the researchers also deciphered how Homer proteins exert their antidepressant effect. They activate surface proteins called AMPA receptors, causing the cell to respond more strongly to stimuli. This makes adaptation and learning easier. If the proteins Homer and AMPA are produced to a lesser extent, as in the brains of people with severe depression, the affected individuals find these processes more difficult.
Conceivable use as a nasal spray
“The therapeutic approach was very successful in the laboratory and in animal models. Now further studies must follow, on possible side effects, the metabolization of the active ingredient and the specific psychiatric use,” says Serchov. “In the long term, it is conceivable that the active ingredient could also be used as a nasal spray. This would deliver it directly to the right brain region, the prefrontal cortex.”
Source: Enhanced mGlu5 signaling in excitatory neurons promotes rapid antidepressant effects via AMPA receptor activation DOI: 10.1016/j.neuron.2019.07.011
www.cell.com/neuron/fulltext/S0896-6273(19)30637-3
University Medical Center Freiburg (D)
InFo NEUROLOGY & PSYCHIATRY 2019; 17(5): 31.
