A new molecular target identified in depression
The discovery of a new mechanism involved in depression 鈥� and a way to target it with a drug as effective as classical antidepressants -- provides new understanding of this illness and could pave the way for treatments with fewer side effects.
In a published in Nature Medicine, a team of scientists at 捆绑SM社区 and France鈥檚 Institut national de la sant茅 et de la recherche m茅dicale (INSERM) examined the biological and molecular mechanisms at play in neurons during treatment with a classical antidepressant.
Conducted simultaneously in humans and mice, the research by Bruno Giros, professor in 捆绑SM社区鈥檚 Department of Psychiatry, and El茅ni Tzavara, Director of Research at INSERM, was designed to show how antidepressants act on two neurotransmitters known to influence mood: serotonin and norepinephrine.
When these neurotransmitters come in contact with receptors located on the surface of neurons, they trigger a series of signalling cascades inside the cell. Thus, much as in a relay race, various molecules pass on instructions, to be delivered to the nucleus, telling it to activate or inactivate the expression of genes involved in various biological functions. Because antidepressants act directly on two multifunctional neurotransmitters, they are accompanied by a number of adverse effects.
In their study, the researchers show that in mice, one can target a single runner in this relay race, Elk-1, a molecule that steps in for the last lap of the race and that appears to be directly involved in depressive disorders.
鈥淲hat鈥檚 interesting and rather new is that we have shown the advantage of targeting signalling modules (a runner) rather than the entire pathway,鈥� explains Giros, who is also a researcher at the Douglas Mental Health University Institute (CIUSSS de l鈥橭uest-de-l鈥櫭巐e-de-Montr茅al). 鈥淭his surgical approach should enable us to avoid the adverse effects of classical antidepressants.鈥�
Towards better and faster treatment?
For about a third of patients suffering from major depressive disorder, the path to healing can prove long because physicians have to find, by trial and error, the appropriate drug and dosage to treat them. Worse still, in approximately 33% of patients, none of the existing drugs have any effect.
鈥淭he drug we鈥檝e tested could also constitute a treatment with fewer failures,鈥� says Giros. 鈥淐lassic antidepressants take up to three weeks to have an effect and this new approach could give quicker response times.鈥�
This potential new drug, which is protected by a patent, was developed by Melkin Pharmaceuticals, a biotech co-founded by Giros.
Giros鈥檚 research has further indicated 聽that 聽Elk-1 shows promise as a therapeutic biomarker for determining which patients are more likely to respond to treatments.
This research was funded by ERA-NET-Neuron, LABEX-Biopsy, the Fondation pour la Recherche sur le Cerveau, Assistance Publique-H么pitaux de Marseille, the Conseil R茅gional d鈥橝quitaine, and the Canadian Institutes of Health Research.
鈥�,鈥� by K. Apazoglou et al., Nature Medicine
