title: Illness Severity, Social and Cognitive Ability, and EEG Analysis of Ten Patients with Rett Syndrome Treated with Mecasermin (Recombinant Human IGF-1).
abstract: 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. 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.
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pini
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Congiu
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Benincasa
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: DiMarco
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bigoni
authors.affiliation: School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Adam H
authors.initials: AH
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Mortimer
authors.affiliation: Trinity College Institute of Neuroscience, College Green, Dublin 2, Ireland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Della-Chiesa
authors.affiliation: School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Leary
authors.affiliation: School of Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Rachel
authors.initials: R
authors.lastname: McNamara
authors.affiliation: Department of Genetics, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.affiliation: Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy; Department of Psychiatry, Trinity College Dublin, College Green, Dublin 2, Ireland; Neuropsychiatric Genetics, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tropea