Molecular Therapy of Melanocortin-4-Receptor Obesity by an Autoregulatory BDNF Vector.

ABSTRACT: Mutations in the melanocortin-4-receptor (MC4R) comprise the most common monogenic form of severe early-onset obesity, and conventional treatments are either ineffective long-term or contraindicated. Immediately downstream of MC4R-in the pathway for regulating energy balance-is brain-derived neurotrophic factor (BDNF). Our previous studies show that adeno-associated virus (AAV)-mediated hypothalamic BDNF gene transfer alleviates obesity and diabetes in both diet-induced and genetic models. To facilitate clinical translation, we developed a built-in autoregulatory system to control therapeutic gene expression mimicking the body's natural feedback systems. This autoregulatory approach leads to a sustainable plateau of body weight after substantial weight loss is achieved. Here, we exa

SUBMITTER: Siu JJ 

PROVIDER: S-EPMC5744069 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature