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SMALL EXTRACELLULAR VESICLES EXPRESSING A DOMINANT NEGATIVE AMPK ALPHA 1 MUTANT FOR USE IN THE TREATMENT OF OBESITY
EP4137148A1
The present invention relates to a population of small extracellular vesicles (sEVs) for use in the treatment of obesity in a subject in need thereof, wherein the sEVs comprise at least one polynucleotide encoding a dominant negative AMP-activated protein kinase alpha 1 (AMPKα1-DN) mutant protein operably linked and under the control of a steroidogenic factor 1 (SF1) promoter, wherein the sEVs are engineered to transiently express in their outer membrane at least one fusion protein comprising the neurotrophic rabies virus (RVG) peptide fused to lysosome-associated membrane protein 2b. Said population is highly safe and effective, as the sEVs, when administered systematically, are capable of exert their effect in the SF1 expressing neurons located in the ventromedial nucleus of the hypothalamus.
The present invention provides a population of small extracellular vesicles (sEVs) capable, when administered systemically, of significantly decreasing the activation levels of AMP-activated protein kinase (AMPK) in SF1 expressing neurons located in the ventromedial nucleus of the hypothalamus (VMH) in comparison to the activation levels of AMPK in untreated SF1 expressing cells, without said decrease being significantly reduced in other SF1 expressing tissues selected from the list consisting of adrenal glands, testicles, or pituitary gland;