Use of spadin for the treatment of depression

Use of spadin for the treatment of
depression
Our reference :
01424-02
Status des brevets
European patent
application
EP07291602.6 filed on
December 21st, 2007
and entitled "Utilisation
du propeptide NTSR3
dans le traitement des
maladies
psychiatriques"
Inventors
Jean MAZELLA
Catherine HEURTEAUX
Marc BORSOTTO
Olivier PETRAULT
Catherine WIDMANN
Status Commercial
Exclusive or nonexclusive licenses
CONTEXT
Depression is the most common of psychiatric illnesses, with prevalence estimates
ranging from 5% to 20% within the general population. The design of effective treatments
for this disorder is a challenging process, and the use of antidepressants has an overall
low clinical efficacy as full remission only occurs in one-third of the patients. Moreover, the
time between initial treatment and beneficial effects is relatively protracted.
TECHNICAL DESCRIPTION
The invention relates to spadin, a natural peptide derived from the neurotensin receptor-3
(NSTR3) that is released in blood. This peptide is able to block TREK-1 channel’s activity,
an attractive pharmacological target for the development of new types of antidepressant
drugs as illustrated by the Star*D study.
Dr Mazella’s team showed that spadin is an efficient antidepressant in mice that acts
much faster than fluoxetine, the most commonly used antidepressant (4 days versus
several weeks). However, this peptide has no effect on stress and anxiety, a feature that
is very well appreciated by psychiatrists.
PK/ADME* data:
The inventors have confirmed that i.p. and i.v. injected peptide goes easily through the
Blood-Brain Barrier.
More recently, they have investigated the effects of spadin on TREK-1 other functions.
Indeed, TREK-1 blockade is known to enhance nociception, epilepsy onset, the probability
of neuronal damages induced by strokes or cardiac function. No such effect has been
observed in mice receiving spadin. In addition, the injection of peptide has no influence on
the food comsuption.
BENEFITS
The advantage of spadin is its rapidity of action as an antidepressant and the lack of side
effects. The peptide is a natural compound and as a consequence can be, in one hand,
rapidly metabolized after triggering its action and, in the other hand, easily modified for
increasing, if necessary, its efficacy.
A delivery system suitable for a chronic administration is currently developed in
collaboration with the company Medincell (Montpellier, France). This program aims at
providing a slow-release formulation of the peptide that will ensure a stable blood
concentration of spadin for 3 consecutive weeks, and thus improve the future
patients’compliance. This work is supported by a grant of the National Agency of
Research (ANR) in the category “Emergence”.
Laboratoires
PUBLICATIONS
Institut de
Pharmacologie
Spadin as a new antidepressant: absence of TREK-1-related side effects.
Moha Ou Maati H, Veyssiere J, Labbal F, Coppola T, Gandin C, Widmann C, Mazella J,
Heurteaux C, Borsotto M. Neuropharmacology. 2012 Jan;62(1):278-88.
Moléculaire et
Cellulaire, a CNRS and
University Artois
Laboratory (UMR 6097),
in Valbonne, France,
www.ipmc.cnrs.fr
Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the
antidepressant drug design.
Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M,
Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G,
Nahon JL, Heurteaux C, Borsotto M. PLoS Biol. 2010 Apr 13;8(4):e1000355.
For further information, please contact us (Ref 01424-02)
Keywords :
Depression Anxiety
Neurotensin Spadin
TREK-1
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