Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome.

ABSTRACT: Individuals with Prader-Willi syndrome (PWS) display developmental delays, cognitive impairment, excessive hunger, obesity, and various behavioral abnormalities. Current PWS treatments are limited to strict supervision of food intake and growth hormone therapy, highlighting the need for new therapeutic strategies. Brain-derived neurotrophic factor (BDNF) functions downstream of hypothalamic feeding circuitry and has roles in energy homeostasis and behavior. In this preclinical study, we assessed the translational potential of hypothalamic adeno-associated virus (AAV)-BDNF gene therapy as a therapeutic for metabolic dysfunction in the Magel2-null mouse model of PWS. To facilitate clinical translation, our BDNF vector included an autoregulatory element allowing for transgene titration

SUBMITTER: Queen NJ 

PROVIDER: S-EPMC9573893 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature