Gene-transfer technology: a preventive neurotherapy to curb obesity, ameliorate metabolic syndrome and extend life expectancy.

Leptin insufficiency at crucial target sites in the hypothalamic circuitries that integrate energy intake and expenditure underlies abnormal rates of fat accumulation. The payload of this "fat burden" is metabolic syndrome, a cluster of life-threatening metabolic afflictions, and a shorter lifespan. Currently available therapies employed to combat obesity have disadvantages such as poor compliance for lifestyle modification or transient effectiveness and undesirable side-effects of pharmacological interventions. Recent studies suggest that neurotherapy comprising a single central administration of recombinant adeno-associated virus vector encoding the leptin gene severely depletes fat and ameliorates the major symptoms of metabolic syndrome for extended periods in rodents. These persistent benefits avert the deleterious impact of the "fat burden" and extend life expectancy. Thus, the novel approach of central gene-transfer technology has distinct advantages over current therapies and has the potential to correct or slow the progression of inherited or acquired hypothalamic diseases.