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Comparison of Serum VEGF, IGF-1, and HIF-1? Levels in Children with Autism Spectrum Disorder and Healthy Controls / F. ?IM?EK in Journal of Autism and Developmental Disorders, 51-10 (October 2021)
[article]
Titre : Comparison of Serum VEGF, IGF-1, and HIF-1? Levels in Children with Autism Spectrum Disorder and Healthy Controls Type de document : Texte imprimé et/ou numérique Auteurs : F. ?IM?EK, Auteur ; Ü I?IK, Auteur ; E. AKTEPE, Auteur ; F. KILIÇ, Auteur ; F. B. ?IRIN, Auteur ; M. BOZKURT, Auteur Article en page(s) : p.3564-3574 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis Child Humans Hypoxia-Inducible Factor 1, alpha Subunit/blood Insulin-Like Growth Factor I/analysis Vascular Endothelial Growth Factor A/blood Autism spectrum disorder Hif-1? Igf-1 Vegf Index. décimale : PER Périodiques Résumé : The aim of this study was to determine whether serum VEGF, IGF-1, and HIF-1? levels differed between Autism Spectrum Disorder (ASD) patients and healthy controls. A total of 40 children with ASD and 40 healthy controls aged 4-12 years were included. Serum levels of VEGF, IGF-1, and HIF-1? were measured using commercial enzyme-linked immunosorbent assay kits. Serum IGF-1 levels were found to be statistically significantly higher in the ASD group than in the control group. Serum HIF-1? levels were borderline significantly lower in the ASD group. There was no statistically significant difference in serum VEGF levels between the two groups. IGF-1 and HIF-1? may play a potential role in the etiopathogenesis of ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04820-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453
in Journal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3564-3574[article] Comparison of Serum VEGF, IGF-1, and HIF-1? Levels in Children with Autism Spectrum Disorder and Healthy Controls [Texte imprimé et/ou numérique] / F. ?IM?EK, Auteur ; Ü I?IK, Auteur ; E. AKTEPE, Auteur ; F. KILIÇ, Auteur ; F. B. ?IRIN, Auteur ; M. BOZKURT, Auteur . - p.3564-3574.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3564-3574
Mots-clés : Autism Spectrum Disorder/diagnosis Child Humans Hypoxia-Inducible Factor 1, alpha Subunit/blood Insulin-Like Growth Factor I/analysis Vascular Endothelial Growth Factor A/blood Autism spectrum disorder Hif-1? Igf-1 Vegf Index. décimale : PER Périodiques Résumé : The aim of this study was to determine whether serum VEGF, IGF-1, and HIF-1? levels differed between Autism Spectrum Disorder (ASD) patients and healthy controls. A total of 40 children with ASD and 40 healthy controls aged 4-12 years were included. Serum levels of VEGF, IGF-1, and HIF-1? were measured using commercial enzyme-linked immunosorbent assay kits. Serum IGF-1 levels were found to be statistically significantly higher in the ASD group than in the control group. Serum HIF-1? levels were borderline significantly lower in the ASD group. There was no statistically significant difference in serum VEGF levels between the two groups. IGF-1 and HIF-1? may play a potential role in the etiopathogenesis of ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04820-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome / A. KOLEVZON in Molecular Autism, 13 (2022)
[article]
Titre : Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 17 p.[article] Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur . - 17 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 17 p.
Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Insulin-Like Growth Factor and Insulin-Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue / Milena CIOANA in Autism Research, 13-6 (June 2020)
[article]
Titre : Insulin-Like Growth Factor and Insulin-Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue Type de document : Texte imprimé et/ou numérique Auteurs : Milena CIOANA, Auteur ; Bernadeta MICHALSKI, Auteur ; Margaret FAHNESTOCK, Auteur Article en page(s) : p.897-907 Langues : Anglais (eng) Mots-clés : Igf-1 IGF-1 receptor autism fusiform gyrus gene expression Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is believed to stem from defects in the establishment and maintenance of functional neuronal networks due to synaptic/spine dysfunction. The potent effects of IGF-1 on synaptic function, maintenance, and plasticity make it a potential target for treating ASD. This polypeptide hormone has proven to have beneficial effects in treating related developmental disorders like Rett syndrome, and its efficacy in ASD is currently being investigated in a pilot study. IGF-1 binds to its receptor (IGF-1R) in neurons and activates mitogen-activated protein kinase and PI3K/Akt signaling to produce biological effects on spine function. The PI3K/Akt pathway is dysregulated in ASD, including idiopathic autism, and is thus believed to play a role in the disorder. Despite this, no study has explored the levels of IGF-1 in the fusiform gyrus of idiopathic autism patients, an area known to be hypoactivated in ASD, and no study has examined IGF-1R in any part of the brain. The present study explored whether IGF-1 or IGF-1R levels are altered in human idiopathic autism. RNA and protein were extracted from post-mortem human fusiform gyrus tissue of normal controls (n = 20) and subjects with idiopathic autism (n = 15). qRT-PCR for IGF-1 and IGF-1R were performed, along with total IGF-1 ELISA and IGF-1R? Western blots. The levels of both IGF-1 and IGF-1R mRNA and protein were equivalent between the two groups, suggesting that although IGF-1 may be useful for ASD treatment, IGF-1 and IGF-1R are not implicated in the pathogenesis of idiopathic autism. Autism Res 2020, 13: 897-907. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: IGF-1 is being tested for the treatment of autism and related disorders. Despite promising results, it is unknown if IGF-1 or its receptor are present in abnormal levels in patients with autism. This study showed that patients with autism have normal levels of IGF-1 and its receptor in the brain, suggesting that although IGF-1 is a promising treatment, disruption of IGF-1 levels or signaling through its receptor does not seem to be a cause of autism. En ligne : http://dx.doi.org/10.1002/aur.2291 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Autism Research > 13-6 (June 2020) . - p.897-907[article] Insulin-Like Growth Factor and Insulin-Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue [Texte imprimé et/ou numérique] / Milena CIOANA, Auteur ; Bernadeta MICHALSKI, Auteur ; Margaret FAHNESTOCK, Auteur . - p.897-907.
Langues : Anglais (eng)
in Autism Research > 13-6 (June 2020) . - p.897-907
Mots-clés : Igf-1 IGF-1 receptor autism fusiform gyrus gene expression Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is believed to stem from defects in the establishment and maintenance of functional neuronal networks due to synaptic/spine dysfunction. The potent effects of IGF-1 on synaptic function, maintenance, and plasticity make it a potential target for treating ASD. This polypeptide hormone has proven to have beneficial effects in treating related developmental disorders like Rett syndrome, and its efficacy in ASD is currently being investigated in a pilot study. IGF-1 binds to its receptor (IGF-1R) in neurons and activates mitogen-activated protein kinase and PI3K/Akt signaling to produce biological effects on spine function. The PI3K/Akt pathway is dysregulated in ASD, including idiopathic autism, and is thus believed to play a role in the disorder. Despite this, no study has explored the levels of IGF-1 in the fusiform gyrus of idiopathic autism patients, an area known to be hypoactivated in ASD, and no study has examined IGF-1R in any part of the brain. The present study explored whether IGF-1 or IGF-1R levels are altered in human idiopathic autism. RNA and protein were extracted from post-mortem human fusiform gyrus tissue of normal controls (n = 20) and subjects with idiopathic autism (n = 15). qRT-PCR for IGF-1 and IGF-1R were performed, along with total IGF-1 ELISA and IGF-1R? Western blots. The levels of both IGF-1 and IGF-1R mRNA and protein were equivalent between the two groups, suggesting that although IGF-1 may be useful for ASD treatment, IGF-1 and IGF-1R are not implicated in the pathogenesis of idiopathic autism. Autism Res 2020, 13: 897-907. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: IGF-1 is being tested for the treatment of autism and related disorders. Despite promising results, it is unknown if IGF-1 or its receptor are present in abnormal levels in patients with autism. This study showed that patients with autism have normal levels of IGF-1 and its receptor in the brain, suggesting that although IGF-1 is a promising treatment, disruption of IGF-1 levels or signaling through its receptor does not seem to be a cause of autism. En ligne : http://dx.doi.org/10.1002/aur.2291 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome / S. SETHURAM in Molecular Autism, 13 (2022)
[article]
Titre : A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : S. SETHURAM, Auteur ; T. LEVY, Auteur ; J. FOSS-FEIG, Auteur ; Danielle B. HALPERN, Auteur ; S. SANDIN, Auteur ; P. M. SIPER, Auteur ; H. WALKER, Auteur ; Joseph D. BUXBAUM, Auteur ; R. RAPAPORT, Auteur ; A. KOLEVZON, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Asd Autism spectrum disorder Growth hormone Igf-1 Insulin-like growth factor-1 Pms Phelan–McDermid syndrome Shank3 Jaguar, Neuren, GW Pharma, and Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan–McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. METHODS: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. RESULTS: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. LIMITATIONS: Results should be interpreted with caution given the small sample size and lack of a placebo control. CONCLUSIONS: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 . En ligne : http://dx.doi.org/10.1186/s13229-022-00485-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 13 (2022) . - 6p.[article] A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / S. SETHURAM, Auteur ; T. LEVY, Auteur ; J. FOSS-FEIG, Auteur ; Danielle B. HALPERN, Auteur ; S. SANDIN, Auteur ; P. M. SIPER, Auteur ; H. WALKER, Auteur ; Joseph D. BUXBAUM, Auteur ; R. RAPAPORT, Auteur ; A. KOLEVZON, Auteur . - 6p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 6p.
Mots-clés : Asd Autism spectrum disorder Growth hormone Igf-1 Insulin-like growth factor-1 Pms Phelan–McDermid syndrome Shank3 Jaguar, Neuren, GW Pharma, and Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan–McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. METHODS: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. RESULTS: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. LIMITATIONS: Results should be interpreted with caution given the small sample size and lack of a placebo control. CONCLUSIONS: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 . En ligne : http://dx.doi.org/10.1186/s13229-022-00485-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459