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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Funcke, JB; Moepps, B; Roos, J; von, Schnurbein, J; Verstraete, K; Fröhlich-Reiterer, E; Kohlsdorf, K; Nunziata, A; Brandt, S; Tsirigotaki, A; Dansercoer, A; Suppan, E; Haris, B; Debatin, KM; Savvides, SN; Farooqi, IS; Hussain, K; Gierschik, P; Fischer-Posovszky, P; Wabitsch, M.
Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.
N Engl J Med. 2023; 388(24): 2253-2261.
Doi: 10.1056/NEJMoa2204041
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Fröhlich-Reiterer Elke
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- Abstract:
- Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.).
- Find related publications in this database (using NLM MeSH Indexing)
- Child - administration & dosage
- Humans - administration & dosage
- Antibodies - administration & dosage
- Homozygote - administration & dosage
- Leptin - genetics
- Obesity, Morbid - genetics
- Signal Transduction - administration & dosage