Abstract | CONTEXT: Recently, in a 4-month proof-of-concept trial, beneficial metabolic effects were reported in non-diabetic children with Berardinelli-Seip congenital lipodystrophy (BSCL); this information prompted us to hypothesize that long-term leptin-replacement therapy might improve or reverse the early complications of the disease in these patients. PATIENTS AND METHODS: A 28-month trial was implemented in eight patients. Efficacy assessment was based on a decrease in serum triglyceride concentrations, and/or a decrease in liver volume and/or an increase in insulin sensitivity of at least 30% respectively. The response was defined as follows: total (3/3 positive criteria), partial (1 or 2/3), or negative (0/3). Anti- leptin antibodies were measured with a radiobinding assay, and a neutralizing effect was assessed in primary cultures of embryonic neurons incubated with an apoptotic agent ( N-methyl-D-aspartate) and the patient serum, with or without leptin. RESULTS: A negative or partial response to treatment was observed in five of eight patients even when leptin dosages were increased. A displaceable leptin binding was detectable in all patients after 2 months of treatment. At 28 months, binding was higher in the patients with a negative response than in the total responders, and it paralleled both the increase in leptin dosage and serum leptin concentrations. Co-incubation of embryonic neurons with serum from two patients with a negative response inhibited the neuroprotective effect of leptin. CONCLUSION: Under leptin therapy, patients with BSCL may develop a resistance to leptin, which could be partly of immunological origin, blunting the previously reported beneficial effects.
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Authors | Jacques Beltrand, Najiba Lahlou, Tifenn Le Charpentier, Guy Sebag, Sofia Leka, Michel Polak, Nadia Tubiana-Rufi, Didier Lacombe, Marc de Kerdanet, Frederic Huet, Jean-Jacques Robert, Didier Chevenne, Pierre Gressens, Claire Lévy-Marchal |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 162
Issue 6
Pg. 1083-91
(Jun 2010)
ISSN: 1479-683X [Electronic] England |
PMID | 20236991
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Neutralizing
- Blood Glucose
- Leptin
- Lipids
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Topics |
- Adolescent
- Antibodies, Neutralizing
(immunology, metabolism)
- Blood Glucose
(metabolism)
- Body Composition
- Child
- Child, Preschool
- Drug Administration Schedule
- Female
- Humans
- Leptin
(administration & dosage, metabolism)
- Lipid Metabolism
- Lipids
(blood)
- Lipodystrophy, Congenital Generalized
(immunology, metabolism, therapy)
- Liver
(metabolism)
- Male
- Patient Selection
- Prospective Studies
- Statistics, Nonparametric
- Treatment Outcome
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