Leptin replacement improves cognitive development

• Published in: PloS one Vol. 3; no. 8; p. e3098
• Main Authors: Paz-Filho, Gilberto J, Babikian, Talin, Asarnow, Robert, Delibasi, Tuncay, Esposito, Karin, Erol, Halil K, Wong, Ma-Li, Licinio, Julio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29-08-2008; Public Library of Science (PLoS)
• Subjects: Abnormalities, Multiple - genetics; Age; Balances (scales); Behavior; Behavioral sciences; Biomedical materials; Body composition; Brain; Central nervous system; Child; Child development; Children; Circadian rhythm; Codons; Cognition; Cognition - drug effects; Cognition - physiology; Cognition Disorders - drug therapy; Cognition Disorders - genetics; Cognitive ability; Developmental Biology/Neurodevelopment; Diabetes and Endocrinology/Neuroendocrinology and Pituitary; Diabetes and Endocrinology/Obesity; Drug dosages; Dyslipidemia; Endocrinology; Excitability; Families & family life; Food; Gene expression; Gene mutation; Genetic aspects; Homeostasis; Hormone Replacement Therapy - methods; Humans; Hyperinsulinemia; Hypertension; Leptin; Leptin - genetics; Leptin - therapeutic use; Male; Medicine; Mental Health/Cognitive Neurology; Mental Health/Developmental and Pediatric Neurology; Mental Health/Eating Disorders; Metabolism; Mutation; Mutation, Missense; Neurons; Neuropeptides; Neuroscience/Cognitive Neuroscience; Neuroscience/Neurodevelopment; Obesity, Morbid - genetics; Patients; Pediatrics and Child Health/Developmental and Pediatric Neurology; Peptides; Physiological aspects; Plasticity (synaptic); Point mutation; Psychiatry; Rodents; Surgical implants; Synaptic plasticity; Weight loss; Los Angeles California; California; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003098

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.
To evaluate the effect of leptin on neurocognitive development.
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.
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.
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.
ClinicalTrials.gov NCT00659828.