Leptin replacement improves cognitive development

Gilberto J Paz-Filho, Talin Babikian, Robert Asarnow, Tuncay Delibasi, Karin Esposito, Halil K Erol, Ma-Li Wong, Julio Licinio, Gilberto J Paz-Filho, Talin Babikian, Robert Asarnow, Tuncay Delibasi, Karin Esposito, Halil K Erol, Ma-Li Wong, Julio Licinio

Abstract

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.

Methodology: 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.

Principal findings: 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.

Trial registration: ClinicalTrials.gov NCT00659828.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Rates of development for DAS…
Figure 1. Rates of development for DAS subtests.
A rate of “1” (vertical axis) indicates typical development (i.e., developmental age equals chronological age). For example, at age 4, performance at the level of a 4 year old would yield a rate of development of 1 (4/4). In contrast, at age 4, a performance at the level of a 3 year old would yield a developmental rate of 0.75 (3/4). Subsequently, a score of

Figure 2. Rates of development for NEPSY…

Figure 2. Rates of development for NEPSY subtests.

A rate of “1” (vertical axis) indicates…

Figure 2. Rates of development for NEPSY subtests.
A rate of “1” (vertical axis) indicates typical development (i.e., developmental age matches chronological age). A score of

Figure 3. Patient before replacement with r-metHuLeptin…

Figure 3. Patient before replacement with r-metHuLeptin at age 5y1m and during treatment at age…

Figure 3. Patient before replacement with r-metHuLeptin at age 5y1m and during treatment at age 7y2m.
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References
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Figure 2. Rates of development for NEPSY…
Figure 2. Rates of development for NEPSY subtests.
A rate of “1” (vertical axis) indicates typical development (i.e., developmental age matches chronological age). A score of

Figure 3. Patient before replacement with r-metHuLeptin…

Figure 3. Patient before replacement with r-metHuLeptin at age 5y1m and during treatment at age…

Figure 3. Patient before replacement with r-metHuLeptin at age 5y1m and during treatment at age 7y2m.
Figure 3. Patient before replacement with r-metHuLeptin…
Figure 3. Patient before replacement with r-metHuLeptin at age 5y1m and during treatment at age 7y2m.

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