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1. WO2019057742 - METHODS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING AUTOPHAGY

Publication Number WO/2019/057742
Publication Date 28.03.2019
International Application No. PCT/EP2018/075286
International Filing Date 19.09.2018
IPC
A61P 35/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
A61P 25/28 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25Drugs for disorders of the nervous system
28for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 9/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
9Drugs for disorders of the cardiovascular system
A61P 37/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
A61P 29/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs (NSAIDs)
A61K 38/17 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
CPC
A61K 38/17
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17from animals; from humans
A61K 39/0005
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
0005Vertebrate antigens
A61K 39/39
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
39characterised by the immunostimulating additives, e.g. chemical adjuvants
C07K 16/18
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
C07K 2317/21
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
20characterized by taxonomic origin
21from primates, e.g. man
C07K 2317/24
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
20characterized by taxonomic origin
24containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) [FR]/[FR]
  • SORBONNE UNIVERSITÉ, [FR]/[FR]
  • UNIVERSITE DE PARIS
Inventors
  • KROEMER, Guido
  • BRAVO-SAN, José Manuel
Agents
  • INSERM TRANSFERT
Priority Data
17306229.020.09.2017EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) METHODS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING AUTOPHAGY
(FR) MÉTHODES ET COMPOSITIONS PHARMACEUTIQUES POUR LA MODULATION DE L'AUTOPHAGIE
Abstract
(EN)
Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets. Accordingly, the present invention relates to methods and pharmaceutical compositions for modulating autophagy based on the modulation of the activity or expression of DBI.
(FR)
L'autophagie est typiquement activée par la famine, permettant aux cellules et aux organismes de mobiliser leurs réserves d'énergie. Il est connu que la modulation pharmacologique de l'autophagie représente un potentiel thérapeutique. Les inventeurs ont démontré ici qu'une protéine qui est libérée à partir de cellules d'une manière non conventionnelle, dépendante de l'autophagie, à savoir, un inhibiteur de la liaison du diazépam (DBI), régule l'autophagie. En particulier, les inventeurs démontrent que le DBI inhibe l'autophagie et que l'apport de DBI recombinant à des souris améliore la glycolyse, améliore la lipogenèse et inhibe l'oxydation d'acide gras. Les inventeurs ont montré que la neutralisation de DBI par un anticorps monoclonal et une immunisation active au moyen d'un dérivé immunogène de DBI provoquant des auto-anticorps induisent l'autophagie et conduisent à des changements métaboliques qui augmentent la perte de poids induite par la famine, réduisent l'apport alimentaire lors de la ré-alimentation, et réduisent le gain de poids en réponse à des régimes hypercaloriques. En conséquence, la présente invention concerne des méthodes et des compositions pharmaceutiques pour moduler l'autophagie sur la base de la modulation de l'activité ou de l'expression de DBI.
Also published as
JP2020516833
Latest bibliographic data on file with the International Bureau