Browsing by Author "Dawson, Geraldine"

Now showing 1 - 14 of 14

Open Access
A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.
(The Journal of pediatrics, 2020-07) Dawson, Geraldine; Sun, Jessica M; Baker, Jennifer; Carpenter, Kimberly; Compton, Scott; Deaver, Megan; Franz, Lauren; Heilbron, Nicole; Herold, Brianna; Horrigan, Joseph; Howard, Jill; Kosinski, Andrzej; Major, Samantha; Murias, Michael; Page, Kristin; Prasad, Vinod K; Sabatos-DeVito, Maura; Sanfilippo, Fred; Sikich, Linmarie; Simmons, Ryan; Song, Allen; Vermeer, Saritha; Waters-Pick, Barbara; Troy, Jesse; Kurtzberg, Joanne
Objective
To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD).
Study design
This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion.
Results
CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power.
Conclusions
Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.
Open Access
A Six-Minute Measure of Vocalizations in Toddlers with Autism Spectrum Disorder
(Autism Research) Tenenbaum, Elena J; Carpenter, Kimberly LH; Sabatos-DeVito, Maura; Hashemi, Jordan; Vermeer, Saritha; Sapiro, Guillermo; Dawson, Geraldine
Open Access
A tablet-based game for the assessment of visual motor skills in autistic children.
(NPJ digital medicine, 2023-02) Perochon, Sam; Matias Di Martino, J; Carpenter, Kimberly LH; Compton, Scott; Davis, Naomi; Espinosa, Steven; Franz, Lauren; Rieder, Amber D; Sullivan, Connor; Sapiro, Guillermo; Dawson, Geraldine
Increasing evidence suggests that early motor impairments are a common feature of autism. Thus, scalable, quantitative methods for measuring motor behavior in young autistic children are needed. This work presents an engaging and scalable assessment of visual-motor abilities based on a bubble-popping game administered on a tablet. Participants are 233 children ranging from 1.5 to 10 years of age (147 neurotypical children and 86 children diagnosed with autism spectrum disorder [autistic], of which 32 are also diagnosed with co-occurring attention-deficit/hyperactivity disorder [autistic+ADHD]). Computer vision analyses are used to extract several game-based touch features, which are compared across autistic, autistic+ADHD, and neurotypical participants. Results show that younger (1.5-3 years) autistic children pop the bubbles at a lower rate, and their ability to touch the bubble's center is less accurate compared to neurotypical children. When they pop a bubble, their finger lingers for a longer period, and they show more variability in their performance. In older children (3-10-years), consistent with previous research, the presence of co-occurring ADHD is associated with greater motor impairment, reflected in lower accuracy and more variable performance. Several motor features are correlated with standardized assessments of fine motor and cognitive abilities, as evaluated by an independent clinical assessment. These results highlight the potential of touch-based games as an efficient and scalable approach for assessing children's visual-motor skills, which can be part of a broader screening tool for identifying early signs associated with autism.
Open Access
Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial.
(Stem cells translational medicine, 2017-05) Dawson, Geraldine; Sun, Jessica M; Davlantis, Katherine S; Murias, Michael; Franz, Lauren; Troy, Jesse; Simmons, Ryan; Sabatos-DeVito, Maura; Durham, Rebecca; Kurtzberg, Joanne
Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood-derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty-five children, median age 4.6 years (range 2.26-5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later. Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated. Significant improvements in children's behavior were observed on parent-report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye-tracking measures of children's attention to social stimuli, indicating that these measures may be useful endpoints in future studies. Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD. Stem Cells Translational Medicine 2017;6:1332-1339.
Open Access
Automatic emotion and attention analysis of young children at home: a ResearchKit autism feasibility study
(npj Digital Medicine, 2018-12) Egger, Helen L; Dawson, Geraldine; Hashemi, Jordan; Carpenter, Kimberly LH; Espinosa, Steven; Campbell, Kathleen; Brotkin, Samuel; Schaich-Borg, Jana; Qiu, Qiang; Tepper, Mariano; Baker, Jeffrey P; Bloomfield, Richard A; Sapiro, Guillermo
Open Access
Computer vision tools for low-cost and noninvasive measurement of autism-related behaviors in infants.
(Autism Res Treat, 2014) Hashemi, Jordan; Tepper, Mariano; Vallin Spina, Thiago; Esler, Amy; Morellas, Vassilios; Papanikolopoulos, Nikolaos; Egger, Helen; Dawson, Geraldine; Sapiro, Guillermo
The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated which promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests that behavioral signs can be observed late in the first year of life. Many of these studies involve extensive frame-by-frame video observation and analysis of a child's natural behavior. Although nonintrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are burdensome for clinical and large population research purposes. This work is a first milestone in a long-term project on non-invasive early observation of children in order to aid in risk detection and research of neurodevelopmental disorders. We focus on providing low-cost computer vision tools to measure and identify ASD behavioral signs based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure responses to general ASD risk assessment tasks and activities outlined by the AOSI which assess visual attention by tracking facial features. We show results, including comparisons with expert and nonexpert clinicians, which demonstrate that the proposed computer vision tools can capture critical behavioral observations and potentially augment the clinician's behavioral observations obtained from real in-clinic assessments.
Open Access
Distance from Typical Scan Path When Viewing Complex Stimuli in Children with Autism Spectrum Disorder and its Association with Behavior
(Journal of Autism and Developmental Disorders) Tenenbaum, Elena J; Major, Samantha; Carpenter, Kimberly LH; Howard, Jill; Murias, Michael; Dawson, Geraldine
Open Access
Electrophysiological Biomarkers Predict Clinical Improvement in an Open-Label Trial Assessing Efficacy of Autologous Umbilical Cord Blood for Treatment of Autism.
(Stem cells translational medicine, 2018-11) Murias, Michael; Major, Samantha; Compton, Scott; Buttinger, Jessica; Sun, Jessica M; Kurtzberg, Joanne; Dawson, Geraldine
This study was a phase I, single-center, and open-label trial of a single intravenous infusion of autologous umbilical cord blood in young children with autism spectrum disorder (ASD). Twenty-five children between the ages of 2 and 6 with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit were enrolled. Safety results and clinical outcomes measured at 6 and 12 months post-infusion have been previously published. The purpose of the present analysis was to explore whether measures of electroencephalography (EEG) theta, alpha, and beta power showed evidence of change after treatment and whether baseline EEG characteristics were predictive of clinical improvement. The primary endpoint was the parent-reported Vineland adaptive behavior scales-II socialization subscale score, collected at baseline, 6- and 12-month visits. In addition, the expressive one word picture vocabulary test 4 and the clinical global impression-improvement scale were administered. Electrophysiological recordings were taken during viewing of dynamic social and nonsocial stimuli at 6 and 12 months post-treatment. Significant changes in EEG spectral characteristics were found by 12 months post-infusion, which were characterized by increased alpha and beta power and decreased EEG theta power. Furthermore, higher baseline posterior EEG beta power was associated with a greater degree of improvement in social communication symptoms, highlighting the potential for an EEG biomarker to predict variation in outcome. Taken together, the results suggest that EEG measures may be useful endpoints for future ASD clinical trials. Stem Cells Translational Medicine 2018;7:783-791.
Open Access
Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.
(PLoS Genet, 2009-06) Bucan, Maja; Abrahams, Brett S; Wang, Kai; Glessner, Joseph T; Herman, Edward I; Sonnenblick, Lisa I; Alvarez Retuerto, Ana I; Imielinski, Marcin; Hadley, Dexter; Bradfield, Jonathan P; Kim, Cecilia; Gidaya, Nicole B; Lindquist, Ingrid; Hutman, Ted; Sigman, Marian; Kustanovich, Vlad; Lajonchere, Clara M; Singleton, Andrew; Kim, Junhyong; Wassink, Thomas H; McMahon, William M; Owley, Thomas; Sweeney, John A; Coon, Hilary; Nurnberger, John I; Li, Mingyao; Cantor, Rita M; Minshew, Nancy J; Sutcliffe, James S; Cook, Edwin H; Dawson, Geraldine; Buxbaum, Joseph D; Grant, Struan FA; Schellenberg, Gerard D; Geschwind, Daniel H; Hakonarson, Hakon
The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11-q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3x10(-5)). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3x10(-4)). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3x10(-39)), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts.
Open Access
Implementing early intervention for autism spectrum disorder: a global perspective.
(Pediatric medicine (Hong Kong, China), 2019-08-23) Franz, Lauren; Dawson, Geraldine
Open Access
Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder.
(Stem cells translational medicine, 2020-10) Sun, Jessica M; Dawson, Geraldine; Franz, Lauren; Howard, Jill; McLaughlin, Colleen; Kistler, Bethany; Waters-Pick, Barbara; Meadows, Norin; Troy, Jesse; Kurtzberg, Joanne
Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 10⁶ cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.
Open Access
Integrating tailored approaches in perioperative care strategies for neurodivergent individuals
(eClinicalMedicine, 2024-10) Moreno-Duarte, Ingrid; Brandsen, Sam; Dawson, Geraldine; Einhorn, Lisa M; Swaminathan, Madhav
Open Access
Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature.
(Scientific reports, 2020-07-02) Simhal, Anish K; Carpenter, Kimberly LH; Nadeem, Saad; Kurtzberg, Joanne; Song, Allen; Tannenbaum, Allen; Sapiro, Guillermo; Dawson, Geraldine
Ollivier-Ricci curvature is a method for measuring the robustness of connections in a network. In this work, we use curvature to measure changes in robustness of brain networks in children with autism spectrum disorder (ASD). In an open label clinical trials, participants with ASD were administered a single infusion of autologous umbilical cord blood and, as part of their clinical outcome measures, were imaged with diffusion MRI before and after the infusion. By using Ricci curvature to measure changes in robustness, we quantified both local and global changes in the brain networks and their potential relationship with the infusion. Our results find changes in the curvature of the connections between regions associated with ASD that were not detected via traditional brain network analysis.
Open Access
White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism.
(Stem cells translational medicine, 2019-02) Carpenter, Kimberly LH; Major, Samantha; Tallman, Catherine; Chen, Lyon W; Franz, Lauren; Sun, Jessica; Kurtzberg, Joanne; Song, Allen; Dawson, Geraldine
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social communication deficits and the presence of restricted interests and repetitive behaviors. We have previously reported significant improvements in behavior, including increased social functioning, improved communication abilities, and decreased clinical symptoms in children with ASD, following treatment with a single infusion of autologous cord blood in a phase I open-label trial. In the current study, we aimed to understand whether these improvements were associated with concurrent changes in brain structural connectivity. Twenty-five 2- to 6-year-old children with ASD participated in this trial. Clinical outcome measures included the Vineland Adaptive Behavior Scales-II Socialization Subscale, Expressive One-Word Picture Vocabulary Test-4, and the Clinical Global Impression-Improvement Scale. Structural connectivity was measured at baseline and at 6 months in a subset of 19 children with 25-direction diffusion tensor imaging and deterministic tractography. Behavioral improvements were associated with increased white matter connectivity in frontal, temporal, and subcortical regions (hippocampus and basal ganglia) that have been previously shown to show anatomical, connectivity, and functional abnormalities in ASD. The current results suggest that improvements in social communication skills and a reduction in symptoms in children with ASD following treatment with autologous cord blood infusion were associated with increased structural connectivity in brain networks supporting social, communication, and language abilities. Stem Cells Translational Medicine 2019;8:138&10.

Browsing by Author "Dawson, Geraldine"

Objective

Study design

Results

Conclusions