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Illness Severity, Social and Cognitive Ability, and EEG Analysis of Ten Patients with Rett Syndrome Treated with Mecasermin (Recombinant Human IGF-1)


Affiliations
1 Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
2 School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland
3 Department of Genetics, Trinity College Dublin, College Green, Dublin 2, Ireland
4 Trinity College Institute of Neuroscience, College Green, Dublin 2, Ireland
5 Department of Psychiatry, Trinity College Dublin, College Green, Dublin 2, Ireland
 

Rett Syndrome (RTT) is a severe neuro developmental 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. The present clinical study examines the disease severity as assessed by clinicians (International Scoring System: ISS), social and cognitive ability assessed by two blinded, independent observers (RSS: Rett Severity Score), and changes in brain activity (EEG) parameters of ten patients with classic RTT and ten untreated patients matched for age and clinical severity. Significant improvement in both the ISS (p = 0.0106) and RSS (p = 0.0274) was found in patients treated with IGF1 in comparison to untreated patients. Analysis of the novel RSS also suggests that patients treated with IGF1 have a greater endurance to social and cognitive testing. The present clinical study adds significant preliminary evidence for the use of IGF-1 in the treatment of RTT and other disorders of the autism spectrum.
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  • Illness Severity, Social and Cognitive Ability, and EEG Analysis of Ten Patients with Rett Syndrome Treated with Mecasermin (Recombinant Human IGF-1)

Abstract Views: 58  |  PDF Views: 7

Authors

Giorgio Pini
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
Laura Congiu
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
Alberto Benincasa
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
Pietro DiMarco
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
Stefania Bigoni
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy
Adam H. Dyer
School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland
Niall Mortimer
Department of Genetics, Trinity College Dublin, College Green, Dublin 2, Ireland
Andrea Della-Chiesa
Trinity College Institute of Neuroscience, College Green, Dublin 2, Ireland
Sean O’Leary
School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland
Rachel McNamara
School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland
Kevin J. Mitchell
Department of Genetics, Trinity College Dublin, College Green, Dublin 2, Ireland
Michael Gill
Department of Psychiatry, Trinity College Dublin, College Green, Dublin 2, Ireland
Daniela Tropea
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy

Abstract


Rett Syndrome (RTT) is a severe neuro developmental 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. The present clinical study examines the disease severity as assessed by clinicians (International Scoring System: ISS), social and cognitive ability assessed by two blinded, independent observers (RSS: Rett Severity Score), and changes in brain activity (EEG) parameters of ten patients with classic RTT and ten untreated patients matched for age and clinical severity. Significant improvement in both the ISS (p = 0.0106) and RSS (p = 0.0274) was found in patients treated with IGF1 in comparison to untreated patients. Analysis of the novel RSS also suggests that patients treated with IGF1 have a greater endurance to social and cognitive testing. The present clinical study adds significant preliminary evidence for the use of IGF-1 in the treatment of RTT and other disorders of the autism spectrum.