The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Omar Khwaja - One of the best experts on this subject based on the ideXlab platform.
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safety pharmacokinetics and preliminary assessment of efficacy of Mecasermin recombinant human igf 1 for the treatment of rett syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Omar Khwaja, Eugenia Ho, Katherine Barnes, Heather M Oleary, Luis M Pereira, Yaron Finkelstein, Charles A NelsonAbstract: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. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.
Kathryn M. Thrailkill - One of the best experts on this subject based on the ideXlab platform.
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Mecasermin rinfabate for severe insulin-like growth factor-I deficiency
Therapy, 2007Co-Authors: Stephen F. Kemp, Kathryn M. ThrailkillAbstract:Recombinant human insulin-like growth factor (rhIGF)-I has been shown to increase growth velocity in children with IGF-I deficiency, either as a result of growth hormone-insensitivity syndrome or IGF-I gene deletion (one case study). There have been adverse events, particularly hypoglycemia, reported with administration of unbound rhIGF-I. In addition, the serum half-life of unbound rhIGF-I is shorter when administered to patients with growth hormone-insensitivity syndrome, who have low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit, than when administered to normal volunteers or to patients with an IGF-I gene deletion (who had normal levels of IGFBP-3). Mecasermin rinfabate, an equimolar mixture of rhIGF-I and the recombinant form of its principal binding protein rhIGFBP-3 (rhIGF-I/rhIGFBP-3), was developed to prolong the half-life and to reduce the risk of acute adverse events (particularly hypoglycemia) associated with administration of rhIGF-I. Published data demonstrate ...
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efficacy and safety of Mecasermin rinfabate
Expert Opinion on Biological Therapy, 2006Co-Authors: Stephen F. Kemp, John L Fowlkes, Kathryn M. ThrailkillAbstract:There has been interest in using recombinant human (rh) insulin-like growth factor (IGF)-I (rhIGF-I) to treat short stature, either alone or in combination with its binding protein (insulin-like growth factor binding protein [IGFBP]-3). IGF-I has been shown to increase growth velocity in children with IGF deficiency, either as a result of growth hormone insensitivity syndrome (GHIS) or IGF gene deletion. However, there have been adverse events, particularly hypoglycaemia, reported with administration of unbound rhIGF-I. In addition, the serum half-life of unbound rhIGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit (ALS), than when administered to normal volunteers or to the patient with an IGF-I gene deletion (who had normal levels of IGFBP-3). iPlex (Mecasermin rinfabate), an equimolar mixture of IGF-I and its binding protein IGFBP-3, was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycaemia) associated with administration of IGF-I. Although there are no published data on the efficacy of Mecasermin rinfabate in treating growth disorders, it does appear that Mecasermin rinfabate has a longer half-life in patients with GHIS than unbound IGF-I, and fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes.
Charles A Nelson - One of the best experts on this subject based on the ideXlab platform.
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safety pharmacokinetics and preliminary assessment of efficacy of Mecasermin recombinant human igf 1 for the treatment of rett syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Omar Khwaja, Eugenia Ho, Katherine Barnes, Heather M Oleary, Luis M Pereira, Yaron Finkelstein, Charles A NelsonAbstract: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. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.
Eugenia Ho - One of the best experts on this subject based on the ideXlab platform.
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safety pharmacokinetics and preliminary assessment of efficacy of Mecasermin recombinant human igf 1 for the treatment of rett syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Omar Khwaja, Eugenia Ho, Katherine Barnes, Heather M Oleary, Luis M Pereira, Yaron Finkelstein, Charles A NelsonAbstract: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. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.
Yaron Finkelstein - One of the best experts on this subject based on the ideXlab platform.
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safety pharmacokinetics and preliminary assessment of efficacy of Mecasermin recombinant human igf 1 for the treatment of rett syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Omar Khwaja, Eugenia Ho, Katherine Barnes, Heather M Oleary, Luis M Pereira, Yaron Finkelstein, Charles A NelsonAbstract: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. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.