Boehringer Ingelheim International Gmbh

Bettina Rudolph

Arnd Steuernagel

Dorothea Ingrid Rudolph

Thomas Ciossek

Karsten Eulenberg

Stefan Jaekel

Guenter Broenner

Funmi Belgore

Christoph Meyer

Stefan Jäkel

Günter Brönner

Dorothea Rudolph

This invention relates to the use of nucleic acid sequences of the MAP kinase-interacting kinase (Mnk) gene family and amino acid sequences encoded thereby, and to using these sequences or effectors of Mnk nucleic acids or polypeptides, particularly Mnk kinase inhibitors and activators, in the diagnosis and treatment of diseases and disorders related to body-weight regulation and thermogenesis. One aspect of the disclosure encompasses methods of identifying an animal or human having an elevated probability of having or developing obesity, the method comprising: (a) obtaining a biological sample from an animal or human subject; and (b) determining from the biological sample whether the animal or human subject has a genetic variant of an Mnk2 and/or Mnk1 gene or a homolog thereof, or an expression product of said Mnk2 and/or Mnk1 gene or homolog thereof, wherein said genetic variant is associated with an elevated probability of having or developing obesity.

Mnk kinase homologous proteins involved in the regulation of energy homeostasis and organelle metabolism

This invention relates to the use of nucleic acid sequences of the MAP kinase-interacting kinase (Mnk) gene family and amino acid sequences encoded thereby, and to using these sequences or effectors of Mnk nucleic acids or polypeptides, particularly Mnk kinase inhibitors and activators, in the diagnosis and treatment of diseases and disorders related to body-weight regulation and thermogenesis. One aspect of the disclosure encompasses methods of identifying an animal or human having an elevated probability of having or developing a pancreatic malfunction, the method comprising: (a) obtaining a biological sample from an animal or human subject; and (b) determining from the biological sample whether the subject has a genetic variant of an Mnk2 and/or Mnk1 gene or a homolog thereof, or an expression product of said Mnk2 and/or Mnk1 gene or homolog thereof, wherein said genetic variant is associated with an elevated probability of having or developing a pancreatic malfunction.

The present invention discloses Mnk homologous proteins regulating the energy homeostasis, the metabolism of triglycerides, and/or is contributing to membrane stability and/or function of organelles, and polynucleotides, which identify and encode the proteins disclosed in this invention. The invention also relates to the use of these sequences in the diagnosis, study, prevention, and treatment of diseases and disorders related to body-weight regulation and thermogenesis, for example, but not limited to, metabolic diseases such as obesity, as well as related disorders such as eating disorder, cachexia, diabetes mellitus, hypertension, coronary heart disease, hypercholesterolemia, dyslipidemia, osteoarthritis, gallstones, and sleep apnea, and disorders related to ROS defence, such as diabetes mellitus, neurodegenerative disorders, and cancer, e.g. cancers of the reproductive organs, and others.

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Hannover, Germany

Bettina Rudolph