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Heather M O'Leary, Walter E Kaufmann, Katherine V Barnes, Kshitiz Rakesh, Kush Kapur, Daniel C Tarquinio, Nicole G Cantwell, Katherine J Roche, Suzanne A Rose, Alexandra C Walco, Natalie M Bruck, Grace A Bazin, Ingrid A Holm, Mark E Alexander, Lindsay C Swanson, Lauren M Baczewski, Juan M Mayor Torres, Charles A Nelson, Mustafa Sahin
Objective: To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design. Methods: Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period...
March 2018: Annals of Clinical and Translational Neurology
Marisela E Dy, Jeff L Waugh, Nutan Sharma, Heather O'Leary, Kush Kapur, Alissa M D'Gama, Mustafa Sahin, David K Urion, Walter E Kaufmann
INTRODUCTION: Hand stereotypies (HS) are a primary diagnostic criterion for Rett syndrome (RTT) but are difficult to characterize and quantify systematically. METHODS: We collected video on 27 girls (2-12 years of age) with classic RTT who participated in a mecasermin trial. The present study focused exclusively on video analyses, by reviewing two five-minute windows per subject to identify the two most common HS. Three raters with expertise in movement disorders independently rated the five-minute windows using standardized terminology to determine the level of agreement...
October 2017: Pediatric Neurology
Kenichiro Furuki, Toshimasa Toyo'oka, Hideto Yamaguchi
RATIONALE: Mecasermin is used to treat elevated blood sugar as well as growth-hormone-resistant Laron-type dwarfism. Mecasermin isolated from inclusion bodies in extracts of E. coli must be refolded to acquire sufficient activity. However, there is no rapid analytical method for monitoring refolding during the purification process. METHODS: We prepared mecasermin drug product, in-process samples during the oxidation of mecasermin, forced-reduced mecasermin, and aerially oxidized mecasermin after forced reduction...
August 15, 2017: Rapid Communications in Mass Spectrometry: RCM
Cyrus Vahdatpour, Adam H Dyer, Daniela Tropea
Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome...
2016: Frontiers in Neuroscience
Giorgio Pini, Laura Congiu, Alberto Benincasa, Pietro DiMarco, Stefania Bigoni, Adam H Dyer, Niall Mortimer, Andrea Della-Chiesa, Sean O'Leary, Rachel McNamara, Kevin J Mitchell, Michael Gill, Daniela Tropea
Rett Syndrome (RTT) is a severe neurodevelopmental disorder characterized by an apparently normal development followed by an arrest and subsequent regression of cognitive and psychomotor abilities. At present, RTT has no definitive cure and the treatment of RTT represents a largely unmet clinical need. Following partial elucidation of the underlying neurobiology of RTT, a new treatment has been proposed, Mecasermin (recombinant human Insulin-Like Growth Factor 1), which, in addition to impressive evidence from preclinical murine models of RTT, has demonstrated safety in human studies of patients with RTT...
2016: Autism Research and Treatment
Leila Haddad, Valiollah Babaeipour, Mohammad Reza Mofid
The isolation of the target protein from inclusion bodies (IBs) is a preliminary step to increase protein titer and to maintain its biological activity. In the present study, the effects of various cell lysis methods and the expression temperature was investigated on the improvement of the subsequent purification steps of mecasermin produced in IB. We also investigated the solubilization profile of the top-notch IB in 6 M guanidine hydrochloride (Gdn-HCl) and 8 M urea at different pH ranges. Mecasermin was expressed at various temperatures (25, 28, 30, and 37 °C) and the Escherichia coli cells were lysed by different cell lysis methods...
November 2015: Research in Pharmaceutical Sciences
Zdenek Frysak, Jan Schovanek, Maurizio Iacobone, David Karasek
Interest in growth hormone (GH) is inextricably linked to the need for in depth understanding of the somatomedins (insulin-like growth factors) which are polypeptides structurally similar to insulin and with broad physiological activity. To date, the most commonly known is Insulin-Like Growth Factor I (IGF-I). Despite considerable current knowledge of IGF-I, however, its bioactivity is incompletely understood. Measurement of IGF-I is of the utmost importance in the diagnosis and treatment of, for example acromegaly and growth hormone deficiency...
September 2015: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
S Jafari, V Babaeipour, H A Eslampanah Seyedi, M Rahaie, M R Mofid, L Haddad, M M Namvaran, J Fallah
Human Insulin-like growth factor 1 (hIGF-1) consists of 70 amino acids in a single chain with three intermolecular disulfide bridges possessing valuable therapeutic effects. To date, numerous variants of specifically engineered hIGF-1 have been produced so as to improve hIGF-1 biological activity, stability and stronger binding to IGF-1 receptor. Mecasermin is one of the modified variants with one amino acid substitution near the N-terminal (T4I) approved for the treatment of growth failure diabetes, wound healing, amyotrophic lateral sclerosis and severe primary IGF-1 deficiency...
November 2014: Research in Pharmaceutical Sciences
Hamidreza Iranpoor, Eskandar Omidinia, Venus Vatankhah, Vahid Gharanjik, Majid Shahbazi
BACKGROUND: Human insulin-like growth factor type 1 (hIGF-1) is a protein consisting of 70 amino acids (MW=7.6 kDa) and mainly synthesized by liver. Mecasermin (Trade name INCRELEX) is the synthetic form of the protein which is used as an effective treatment for particular disorders such as short stature, type 1 and 2 diabetes, and wound healing. Current study was aimed to investigate the expression of human insulin-like growth factor type1 in Escherichia coli (E. coli) BL21 (DE3) expression system in order to produce an active recombinant form of the protein...
July 2015: Avicenna Journal of Medical Biotechnology
Diego Gutiérrez-Fernández, Álvaro Moreno-Ancillo, Antonio Foncubierta-Fernández, Isabel López-Martínez, Alfonso Lechuga-Sancho, María José Fernández-Anguita
No abstract text is available yet for this article.
June 2015: Annals of Allergy, Asthma & Immunology
Jun Ren, Piero Anversa
Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases...
February 15, 2015: Biochemical Pharmacology
Jay Cohen, Sandra Blethen, Joyce Kuntze, Susan L Smith, Kathleen G Lomax, Puthenpurackal M Mathew
Growth failure associated with severe primary insulin-like growth factor 1 (IGF-1) deficiency (SPIGFD), a condition defined as basal IGF-1 standard deviation score (SDS) less than or equal to -3 and height SDS less than or equal to -3 in a child with normal or elevated levels of growth hormone, can be successfully treated with the recombinant human IGF-1 mecasermin. In this review, we describe the most safe and effective way to use mecasermin in the treatment of patients with SPIGFD, including how to initiate dosing, key side effects, and how to monitor treatment...
March 2014: Drugs in R&D
Omar S Khwaja, Eugenia Ho, Katherine V Barnes, Heather M O'Leary, Luis M Pereira, Yaron Finkelstein, Charles A Nelson, Vanessa Vogel-Farley, Geneva DeGregorio, Ingrid A Holm, Umakanth Khatwa, Kush Kapur, Mark E Alexander, Deirdre M Finnegan, Nicole G Cantwell, Alexandra C Walco, Leonard Rappaport, Matt Gregas, Raina N Fichorova, Michael W Shannon, Mriganka Sur, Walter E Kaufmann
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires...
March 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
B García Medrano, P Barrio Sanz, C Simón Pérez, A León Andrino, M Garrosa García, M A Martín Ferrero, M J Gayoso Rodríguez
INTRODUCTION: This project aims to study the regeneration of non-repairable lesions of peripheral nerve by muscle grafts enhanced with growth factors. MATERIAL AND METHODS: The experiment was carried out in two phases. The first one compared direct suture of a critical defect in the sciatic nerve of ten rats, with the interposition of autologous muscle graft, denatured by heat, in another ten. The second phase compared ten rats with nerve repair using an acellular muscle graft, with injection of 2cc of IGF-1 (10mg/ml mecasermin, Injectable solution) into the acellular graft of another ten...
May 2013: Revista Española de Cirugía Ortopédica y Traumatología
Hanane Latrech, Albane Simon, Jacques Beltrand, Jean-Claude Souberbielle, Ghizlane Belmejdoub, Michel Polak
BACKGROUND: Laron syndrome is caused by a mutation in the growth hormone (GH) receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe short stature, and early hypoglycemia. We report a case with postprandial hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement therapy. METHODS: A Moroccan girl referred for short stature at 7 years and 8 months of age had dwarfism [height, 78 cm (-9 SDs); weight, 10 kg (-4 SDs)], hypoglycemia, and truncal obesity...
2012: Hormone Research in Pædiatrics
Carlo Rinaldi, Laura C Bott, Ke-lian Chen, George G Harmison, Masahisa Katsuno, Gen Sobue, Maria Pennuto, Kenneth H Fischbeck
Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by polyglutamine expansion in the androgen receptor. Patients develop slowly progressive proximal muscle weakness, muscle atrophy and fasciculations. Affected individuals often show gynecomastia, testicular atrophy and reduced fertility as a result of mild androgen insensitivity. No effective disease-modifying therapy is currently available for this disease. Our recent studies have demonstrated that insulinlike growth factor (IGF)-1 reduces the mutant androgen receptor toxicity through activation of Akt in vitro, and spinal and bulbar muscular atrophy transgenic mice that also overexpress a noncirculating muscle isoform of IGF-1 have a less severe phenotype...
December 6, 2012: Molecular Medicine
Silvia Marín, Paula Casano-Sancho, Nancy Villarreal-Peña, Giorgia Sebastiani, Sergio Pinillos, Belén Pérez-Dueñas, Vivian Hwa, Ron G Rosenfeld, Lourdes Ibáñez
BACKGROUND: Primary growth hormone insensitivity (GHI) and triple A syndrome are rare autosomal recessive disorders. CASE REPORT: The patient, a 12-year-old boy from consanguineous parents, was referred for short stature at the age of 7 years (height: -5.4 SD score). He had low serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 and a blunted IGF-I response to recombinant human GH; molecular analysis of the GH receptor disclosed a homozygous A(-1)→G(-1) at the 5' pseudoexon 6Ψ splice site...
2012: Hormone Research in Pædiatrics
Elżbieta Petriczko, Beata Wikiera, Anita Horodnicka-Józwa, Katarzyna Marcinkiewicz, Justyna Szmit-Domagalska, Andrzej Kędzia, Julia Durzyńska, Justyna Broniarczyk, Bartosz Gabryelczyk, Anna Noczyńska, Mieczysław Walczak
Growth deficiency is one of the most frequent causes of referral to Endocrinology Outpatient Clinic. IGF-1 (insulin-like growth factor 1) deficiency is one of the rarest causes of short stature. In 2009 in Poland a therapeutic programme was set up for children with severe primary IGF-1 deficiency. The authors present the data of three first polish patients qualified for the rhIGF-1 (recombinant human insulin-like growth factor 1) - mecasermin. The authors conclude that the treatment with rhIGF-1 significantly improves growth velocity in patients with IGF-1 deficiency...
2011: Pediatric Endocrinology, Diabetes, and Metabolism
A Tomillero, M A Moral
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tocilizumab, Tositumomab/iodine (I131) tositumomab, Trabectedin, TransVax™ hepatitis C vaccine; Ustekinumab; V-260, Valspodar, Varenicline tartrate, VCL-IPT1, Vildagliptin, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VRC-HIVDNA016-00-VP; Yttrium 90 (90Y) ibritumomab tiuxetan, Yttrium Y90 Epratuzumab; Zibotentan, Zotarolimus-eluting stent...
November 2010: Methods and Findings in Experimental and Clinical Pharmacology
A Tomillero, M A Moral
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine hydrochloride; Sertindole, Sivelestat sodium hydrate, Sorafenib, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tafluprost, Telithromycin, Temsirolimus, Tenofovir disoproxil fumavate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Ticagrelor, Tigecycline, Tipranavir, Tirapazamine, Trimetrexate; Ulipristal acetate; Valganciclovir hydrochloride, Vicriviroc, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan...
December 2010: Methods and Findings in Experimental and Clinical Pharmacology
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