Processing

Please wait...

Settings

Settings

Goto Application

1. WO2022136417 - PULSATIVE GNRH ADMINISTRATION FOR TREATING FOOD INTAKE RELATED DISORDERS

Publication Number WO/2022/136417
Publication Date 30.06.2022
International Application No. PCT/EP2021/087066
International Filing Date 21.12.2021
IPC
A61K 38/09 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
08Peptides having 5 to 11 amino acids
09Luteinising hormone-releasing hormone ; Related peptides
A61P 3/04 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
3Drugs for disorders of the metabolism
04Anorexiants; Antiobesity agents
A61K 31/7105 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7088Compounds having three or more nucleosides or nucleotides
7105Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
CPC
A61K 31/7105
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7088Compounds having three or more nucleosides or nucleotides
7105Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 38/09
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
08Peptides having 5 to 11 amino acids
09Luteinising hormone-releasing hormone [LHRH] ; , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
A61P 3/04
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
3Drugs for disorders of the metabolism
04Anorexiants; Antiobesity agents
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • UNIVERSITÉ DE LILLE [FR]/[FR]
  • CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE LILLE [FR]/[FR]
  • CENTRE HOSPITALIER D'ARRAS, [FR]/[FR]
  • CHUV CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS, [CH]/[CH]
Inventors
  • PREVOT, Vincent
  • PITTELOUD, Nelly
  • GIACOBINI, Paolo
  • LEYSEN, Valérie
  • SILVA, Mauro Sérgio Batista
  • FLORENT, Vincent
  • IMBERNON, Monica
Agents
  • INSERM TRANSFERT
Priority Data
20306660.022.12.2020EP
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) PULSATIVE GNRH ADMINISTRATION FOR TREATING FOOD INTAKE RELATED DISORDERS
(FR) ADMINISTRATION PULSATILE DE GNRH POUR LE TRAITEMENT DE TROUBLES LIÉS À L'INGESTION D'ALIMENTS
Abstract
(EN) The present invention relates to the pulsatile administration of the gonadotropin- releasing hormone (GnRH) for the treatment of food intake related disorder related disorder such as obesity (overeating) and anorexia (undereating). The inventors demonstrated that a population of mutant mice expressing BoNT/B in GnRH neurons (Gnrh::cre;iBot overweight), in which the GnRH release is inhibited, did not only fail to reach puberty onset and showed hypogonadotropic hypogonadism, but also developed overweight and hyperleptinemia. Unexpectedly, they found that the increase in body weight in mutant mice persisted in adulthood despite a significant decrease in food intake. Using a mouse model of obesity inventors observed an altered pattern of pulsatile LH secretion and that the frequency of LH pulses is inversely correlated to body weight and adiposity demonstrating that the heavier the animals were getting the more the GnRH/LH pulsatile pattern was altered. The present inventors further demonstrated that pulsatile GnRH treatment can allow to restore a control/lean pattern of GnRH/LH release in obese mice, and that this pulsatile administration of a "lean pattern" of native GnRH peptide in obese mice normalized their cumulative food intake to levels comparable with lean mice.
(FR) La présente invention concerne l'administration pulsatile de l'hormone de libération des gonadotrophines (GnRH) pour le traitement d'un trouble lié à l'ingestion d'aliments, tel que l'obésité (hyperphagie) et l'anorexie (sous-alimentation). Les inventeurs ont démontré qu'une population de souris mutantes exprimant BoNT/B dans des neurones GnRH (Gnrh::cre;iBot surpoids), dans lesquelles la libération de GnRH est inhibée, n'est pas parvenue à atteindre le déclenchement de la puberté et a montré un hypogonadisme hypogonadotrophique, mais a de surcroît développé un surpoids et une hyperleptinémie. De manière inattendue, il a été découvert que l'augmentation du poids corporel chez des souris mutantes persiste à l'âge adulte malgré une diminution significative de l'ingestion d'aliments. En utilisant un modèle murin d'obésité, les inventeurs ont observé un profil modifié de sécrétion de LH pulsatile et que la fréquence des pulsations LH est inversement corrélée au poids corporel et à l'adiposité, démontrant que plus les animaux devenaient lourds plus le profil pulsatile de GnRH/LH était modifié. Les présents inventeurs ont en outre démontré que le traitement de GnRH pulsatile peut permettre de restaurer un profil témoin/maigre de libération de GnRH/LH chez des souris obèses, et que cette administration pulsatile d'un "profil maigre" du peptide de GnRH natif chez des souris obèses normalise leur ingestion d'aliments cumulée à des niveaux comparables à celle des souris maigres.
Latest bibliographic data on file with the International Bureau