New perspectives for the depression treatment

An international collaboration1 headed by Eleni Tzavara, within Bruno Giros' team2, has identified the Elk-1 protein as a prognostic marker for depression resistant to conventional treatments. This result, published in Nature Medicine3, was obtained by use of several complementary approaches: clinical studies on two groups of patients suffering from depression, analysis of post-mortem brain tissue and the study of animal models.

The overall results show that (i) increased expression of Elk-1 is associated with depression, (ii) increasing Elk-1 is sufficient to induce depressive behaviour and (iii) conversely, inhibition of signalling via Elk-1 has an antidepressant effect.

The novel tool used to induce the antidepressant effect is a molecule patented4 by Jocelyne Caboche and Peter Vanhoutte5 (IBPS), and licensed by MElkin Pharmaceuticals.

Depression is the most common psychiatric illness; in France it affects more than two million people each year, of which 30% are resistant to conventional treatments. These results open new therapeutic avenues and potential for new treatments of this very serious disease.

The project was funded in part by the Fondation FondaMental (see press release).


1. Assistance Publique-Hôpitaux de Marseille, de l’Institut de Neurosciences de la Timone, de l’Institut universitaire en santé mentale Douglas et de l’Université Paris-Descartes

2. Physiopathology of Psychiatric Diseases

3. Antidepressive effects of targeting ELK-1 signal transduction K Apazoglou, et al. Nature Medicine 2018, May 7. doi: 10.1038/s41591-018-0011-0

4. Caboche J, Caboche J, Vanhoutte P, E Tzavara, B Giros « Pepsignal in depression and mood disorders »(EP 08 305 636.6 worldwide extension in 2010 : WO2010/037841) licencié à la société MElkin Pharmaceuticals

Caboche J, Vanhoutte P « Pepsignal » (N°05 290 363.0 ; 2006 PCT extension ; WO : 0872 242 licencié à la société MElkin Pharmaceuticals

5. Neuronal Signaling and Gene Regulation

Elk-1 is highly expressed in the dentate gyrus of the hippocampus. Co-detection of mRNA elk1 (red) and vglut1 (green); nuclear marking DAPI (blue), mouse coronal section; copyright: Sylvie Dumas, Oramacell, Paris, France.