Our Research has 3 Aims:
1. To conduct longitudinal neuroimaging and deep phenotyping of infants to identify early markers and therapeutic targets for autism, Fragile X syndrome, Down syndrome, and Angelman syndrome.
We published the first MRI study to longitudinally measure brain growth trajectories in infants prior to their diagnosis of autism, which demonstrated that brain enlargement in autism is detectable in infancy. Additionally, in three independent studies and cohorts of children, we replicated the consistent finding that infants and toddlers who were diagnosed with autism had excessive volume of cerebrospinal fluid (CSF) surrounding the brain as early as 6 months of age, preceding the onset of diagnostic symptoms.
2. To reverse-translate these findings in children to mechanistic studies in animal models and in vitro cellular models.
Dr. Shen is P.I. of a new 5-year NIH-funded study, which has assembled a team of clinical and basic scientists to study early pathophysiology of CSF and its downstream effects on brain development – using neuroimaging in infants with NDDs and mechanistic studies in mouse models of these NDDs.
3. To forward-translate this research to clinical trials delivering novel therapeutics to individuals with neurodevelopmental disabilities (NDDs).
The CIDD Clinical Trials Program (Co-Directors Jamie Capal & Mark Shen) is conducting several sponsored clinical trials and studies, collecting CSF samples for biomarker discovery, obtaining sleep and EEG measures, and delivering novel gene-based therapies via CSF to individuals with NDDs.
Recruiting Infants 0-6 mo. with Fragile X Syndrome (FXS) & Angelman Syndrome (AS)
For a new 5-year NIH-funded study of brain development & CSF physiology
The Shen lab is recruiting for a study of brain development in babies with Fragile X syndrome (FXS) and Angelman syndrome (AS). These babies will be compared to infants at higher likelihood for autism, infants with typical development, and infants with Down syndrome.
Previous studies by our team have shown that infants who develop autism have abnormally excessive volumes of cerebrospinal fluid (CSF) surrounding the brain (Shen et al., 2013; 2017; 2018). This excessive amount of CSF was detectable with MRI by 6 months of age, prior to diagnosis, and before the onset of behavioral symptoms. In this new study, we will be recruiting a cohort of babies with FXS and AS to determine the relationships between CSF measured by MRI, brain and behavioral development – comparing FXS, AS, autism, Down syndrome, and typical development.
Babies will undergo a noninvasive MRI brain scan starting at 6 months of age, with a follow-up visit at 24 months of age. Brain scans will be conducted during natural sleep (no anesthesia or sedation). The child’s behavioral, cognitive, and motor abilities will also be assessed, and a copy of the behavioral and MRI reports will be provided to the parents. The goal of this research is to understand the earliest detectable neurological biomarkers to improve early detection and inform potential treatments for neurodevelopmental disabilities.
All travel costs to Chapel Hill, NC will be covered by the study – including airfare, hotel, rental car, and meals. Families will be compensated up to $200 per visit for participating in this study. For more information or to participate in the study, please email shenlab@unc.edu or call the study coordinator, Zumin Chen, at (919) 966-8032.
Recruiting Infants with an older sibling with Autism & Infants with Down Syndrome
For the Infant Brain Imaging Study (IBIS)
The Infant Brain Imaging Study (IBIS) is one of ten NIH Autism Centers of Excellence (ACE) in the United States — a network of 10 universities, with UNC being the lead site. IBIS uses the most advanced brain imaging technology to examine brain structure and function during the important period in development from 6 to 24 months of age. In previous work, IBIS researchers demonstrated that specific findings on MRI scans in children as young as 6 months of age can accurately predict which children will later be diagnosed with autism. IBIS has also identified behaviors that indicate a high likelihood for a later autism diagnosis. IBIS is currently enrolling: infants with an older sibling with ASD; infants with an older sibling with typical development; and infants with Down syndrome.
Clinical Trials for Angelman Syndrome
Angelman syndrome (AS) is a genetic developmental disorder that primarily affects the nervous system and causes delayed development, intellectual disability, and issues with speech, motor, and sleep. AS is caused by loss of function of the maternal copy of the UBE3A gene, located on chromosome 15. The CIDD Clinical Trials Program (co-directed by Drs. Jamie Capal and Mark Shen) is conducting two Phase 1/2A clinical trials aimed at evaluating the safety and tolerability of genetic treatments to restore the function of UBE3A. For more info, please contact Hannah Riehl, the CIDD Clinical Trials Program Supervisor.