Leptin replacement improves cognitive development.
BACKGROUND
Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown.


OBJECTIVE
To evaluate the effect of leptin on neurocognitive development.


METHODS
A 5-year-old boy with a nonconservative missense leptin gene mutation (Cys-to-Thr in codon 105) was treated with recombinant methionyl human leptin (r-metHuLeptin) at physiologic replacement doses of 0.03 mg/kg/day. Cognitive development was assessed using the Differential Ability Scales (DAS), a measure of general verbal and nonverbal functioning; and selected subtests from the NEPSY, a measure of neuropsychological functioning in children.


RESULTS
Prior to treatment, the patient was morbidly obese, hypertensive, dyslipidemic, and hyperinsulinemic. Baseline neurocognitive tests revealed slower than expected rates of development (developmental age lower than chronological age) in a majority of the areas assessed. After two years, substantial increases in the rates of development in most neurocognitive domains were apparent, with some skills at or exceeding expectations based on chronological age. We also observed marked weight loss and resolution of hypertension, dyslipidemia and hyperinsulinemia.


CONCLUSIONS
We concluded that replacement with r-metHuLeptin is associated with weight loss and changes in rates of development in many neurocognitive domains, which lends support to the hypothesis that, in addition to its role in metabolism, leptin may have a cognitive enhancing role in the developing central nervous system.


BACKGROUND
ClinicalTrials.gov NCT00659828.
Paz-Filho
Gilberto J
GJ
Department of Psychiatry and Behavioral Sciences, Center for Pharmacogenomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Babikian
Talin
T
Asarnow
Robert
R
Delibasi
Tuncay
T
Esposito
Karin
K
Erol
Halil K
HK
Wong
Ma-Li
ML
Licinio
Julio
J