title: Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist.
abstract: Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin. In such patients, adrenal insufficiency must be treated with hydrocortisone early in life. No effective pharmacologic treatments have been available for the hyperphagia and obesity that characterize the condition. In this investigator-initiated, open-label study, two patients with proopiomelanocortin deficiency were treated with setmelanotide, a new melanocortin-4 receptor agonist. The patients had a sustainable reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in Patient 1 and 20.5 kg after 12 weeks in Patient 2).
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Peter
authors.initials: P
authors.lastname: Kühnen
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Oliver
authors.initials: O
authors.lastname: Blankenstein
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Keith
authors.initials: K
authors.lastname: Gottesdiener
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Lea L
authors.initials: LL
authors.lastname: Martini
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Knut
authors.initials: K
authors.lastname: Mai
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.affiliation: From the Institute for Experimental Pediatric Endocrinology (P.K., O.B., H.K.), the Department of Pediatric Endocrinology and Diabetes (S.W., A.G.), the Department of Endocrinology, Diabetes, and Nutrition and Charité Center for Cardiovascular Research (K.M.), and the Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science (U.B.-P.), Charité-Universitätsmedizin Berlin, and the Clinical Research Unit, Berlin Institute of Health (K.M.) - all in Berlin; the Institute of Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, Université Pierre et Marie Curie, Unité Mixte de Recherche Scientifique 1166, Paris (K.C., L.L.M.); and Rhythm Pharmaceuticals, Boston (K.G.).
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
mesh_terms: D000328:Adult; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006963:Hyperphagia / Q000188:drug therapy* / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000235:genetics; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D010865:Pilot Projects; D011333:Pro-Opiomelanocortin / Q000172:deficiency* / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D055815:Young Adult; D000521:alpha-MSH / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; C579663:setmelanotide; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin