Nelson Laboratory | Neurodevelopmental Disorders | Rare Genetic Disorders

Neural Correlates of Rett Syndrome and Related Disorders

Brief Description
The purpose of this research study is to gain a greater understanding of how the brains of children with Rett syndrome and related disorders process sensory information in comparison to children who are typically developing. The goal of this project is to test tools that may be used to measure the effectiveness of future treatments and play a role in both research and clinical trials.

Eligibility for Study Participation
We are currently recruiting individuals aged 2 months to 24 years old who have a clinical diagnosis of Rett syndrome with a MECP2 variant, MECP2 Duplication, CDKL5, FOXG1, or who are typically developing and within the age range.

Participation Details
If you decide to participate in this study, which has a longitudinal design, it will involve 3 visits to the lab (once a year for three years)*. Visits to the lab may be coordinated with clinic visits here at Boston Children’s Hospital and will be scheduled at times that are convenient for you and your child. Visits will last approximately 2 hours and parents will be with their child at all times. *Participants with CDKL5 who decide to participate are asked to visit the lab for one additional study visit 6 months after the initial visit. As a result, CDKL5 participants and their families will visit the lab a total of 4 times over the course of 3 years.

Research Contact: LCNclinicalstudies@childrens.harvard.edu (Nelson Laboratory)

Full Description
Currently, methods for measuring neural function in those with Rett syndrome and related disorders are limited. These methods are urgently needed so that researchers can learn more about how to treat these neurodevelopmental disorders. One method used to better understand how the brain functions in Rett syndrome and related disorders is through the use of an EEG (electroencephalogram). EEG and related tests record the activity of the brain at rest as well as in response to different stimuli. They measure how the brain processes sensory information through the use of a stretchy, non-invasive cap that collects electrical activity from the brain. Our goal is to gain greater information about how the brains of individuals with these syndromes process sensory information. These tools may be used as measures of treatment in clinical trials and to inform future research on these rare syndromes.


Neural Markers of Fragile X Syndrome

Brief Description
The purpose of this study is to improve our understanding of how differences in brain activity affect learning, language, and behavior in children with Fragile X Syndrome (FXS). Currently there is no effective treatment for FXS. Our goal is to find brain markers that predict cognitive, language, and behavioral difficulties in young children with FXS, and to better understand differences in brain activity between children with and without FXS.

Eligibility for Study Participation

  • Boys or girls 32-84 months old with a diagnosis of Fragile X Syndrome based on full mutation of the FMR1 gene.
  • Boys or girls 32-84 months old who are typically developing.

Participation Details This study involves a single visit to the lab. Each visit will last about 3-4 hours. These visits can be scheduled at your convenience during the day or the weekend.

Research Contact: FXSNeuralMarkers@childrens.harvard.edu or call 617-355-4373

Full Description
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability impacting 1 in 4,000 boys and 1 in 6,000 girls. In addition to cognitive deficits, children with FXS often struggle with significant language delays and behavioral challenges, and nearly half of all individuals meet criteria for Autism Spectrum Disorder (ASD). Currently there is no effective treatment for FXS. Animal models of FXS have led to greater understanding of the neurobiology of the disorder, and identified key drug targets that improve cognitive and behavioral phenotypes. Despite extensive research in animal models, only a handful of studies have investigated brain activity and function in children with FXS, presenting a huge roadblock in translating lab-developed therapeutics to patients. This study aims to identify and characterize brain-based markers that predict cognitive, language, and behavioral deficits in young children with FXS. We will use EEG (a low cost, non-invasive technique) to measure brain activity in response to sensory stimuli, and correlate this with a range of cognitive, language, and behavioral measures. The brain-based markers will then be used in future clinical trials as objective measures for targeted outcomes. Results from this study should improve our understanding of the neural mechanisms that underlie some of the core ASD symptoms and comorbidities seen in FXS.


ASD and Tuberous Sclerosis Complex - JASPER Intervention

Brief description
This study will investigate whether a behavioral intervention can improve social communication skills in infants with TSC, with the overarching goal of lessening symptomatology related to ASD. Research has shown that early intervention improves cognitive and behavioral outcomes in children with atypical development. The proposed intervention adapts a parent-mediated intervention that has successfully improved outcomes in toddlers with idiopathic ASD. In addition to testing the primary effects of this early intervention on developmental outcomes of infants with TSC, we also will use electrophysiological (EEG) methods to examine low level visual processing, face processing and resting state EEG oscillations prior to and after intervention.

Eligibility for Study Participation

  • Infants between 12-36 months of age who have a clinical diagnosis of Tuberous Sclerosis Complex (TSC)
  • English is primary language

Participation Details
Participation requires attending parent-mediated behavioral intervention classes at Boston Children’s Hospital. Participants will take part in four in person and eight remote 60 minute sessions over the course of 12 weeks. Participants are also given behavioral assessments before entry into behavioral intervention, after exiting intervention, and at a follow up visit.

Research Contact: tscjasper@childrens.harvard.edu or call: (857) 218-3010

Full Description
Infants with Tuberous Sclerosis Complex (TSC) are at high risk for neurodevelopmental disabilities, including autism spectrum disorder (ASD) and intellectual disability (ID). In a recent prospective study of infants with TSC, we found that as early as 6 months of age, infants demonstrated delays in non-verbal behaviors critical for the development of social communication skills, and that by 12 months these delays generalized to both verbal and non-verbal cognition. Moreover, a decline in non-verbal cognition over the second two years of life predicted the development of ASD. Based on this clear evidence of early delays, we propose to investigate whether a behavioral intervention can improve social communication skills in infants with TSC, with the overarching goal of lessening symptomatology related to ASD.


A Randomized Double-Blind Controlled Trial of Everolimus in Children and Adolescents with PTEN Mutations

Brief description
The main goals of this study are to determine the safety and efficacy of Everolimus on neurocognitive and social deficits in patients with PTEN. The primary neurocognitive endpoints are working memory, processing speed, and fine motor skills. Currently, there are no effective therapies for individuals with PTEN that targets these core features. Other exploratory objectives include determining the effect of the medication on participants’ microbiome and electroencephalography (EEG) measures. We are also looking into protein biomarkers of PTEN.

Eligibility for Study Participation

  • Males and females between 5 and 45 years of age with a confirmed PTEN mutation and an IQ at or above 50 are eligible for this study.
  • Patients must also meet a series of safety criteria, which is determined by medical history and some lab work.

Participation Details
This study involves a blinded phase and an open label phase. In the blinded phase, patients will come to the study site 5 times in approximately 6 months. Three of these visits (baseline, month 3, and month 6) will include optional EEG assessments that will be done in the lab. The open label phase is available to participants who receive placebo in the blinded phase. The open label phase will consist of 3 more study site visits, 2 of which will include the EEG assessments. Both phases will have scheduled phone calls so study staff can check in with patients and families. Visits vary in length and can take between 2 and 8 hours. These visits can be scheduled at your convenience during the weekdays.

Research Contact: Amelia.Diplock@childrens.harvard.edu, 617-919-1476

Full Description
Patients diagnosed with PTEN Hamartoma Syndrome often have cognitive deficits such as language delays, behavioral challenges, and comorbid Autism Spectrum Disorder (ASD). PTEN syndrome is associated with overactivity in the mTOR pathway. For this reason, the study is looking at the effect of Everolimus, an mTOR inhibitor, on the neurocognitive deficits often seen in patients diagnosed with PTEN. The study is hoping to see positive effects of the medication on working memory, processing speed, and fine motor skills.


JASPER Intervention in Down Syndrome

Brief description
This study will investigate whether a behavioral intervention called JASPER (Joint Attention Symbolic Play Engagement Regulation) can help young children with Down syndrome with their development. Specifically, the study will examine whether JASPER can improve how well children with Down syndrome pay attention, interact with their parents, and adjust their emotions and behavior.

Eligibility for Study Participation

  • Infants between 36-48 months of age who have Down syndrome
  • Parents must be available to participate in all of the intervention and study sessions
  • English is primary language

Participation Details
Participation lasts for 6 months total and involves 1) parent surveys (at home and during visits), 2) 12 weekly visits to the hospital for behavioral assessments, intervention sessions and EEG (brain activity measurements), and 3) weekly phone/video chat check-ins from home.

Research Contactdownsyndrome.research@childrens.harvard.edu or 617-919-6435.

Full description

Research has shown that early targeted behavior interventions have been linked to improved outcomes in cognitive and behavioral functioning for children with Down syndrome. This study will build off JASPER interventions that have already been shown to successfully improve outcomes in toddlers with diagnosed Autism Spectrum Disorder (ASD) and a wide range of developmental abilities. JASPER is individualized and modified based on a child’s skills and behavior. Therefore, it is expected that it may be a particularly effective intervention for children with Down syndrome who have varying levels of developmental skills and social engagement. Developmental outcomes for this study will be measured using behavioral assessments, parent surveys, and electrophysiological (EEG) methods.