Kennedy Krieger Institute Intellectual and Developmental Disabilities Research Center

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/behavior-science-core-objectives

Keywords Subject training for research protocols; fMRI; project development; experimental design; behavioral training; intellectual disabilities; behavior analysis; neuropsychology consultation; movement study; motor learning

Description

The Behavior Science Core provides IDDRC investigators with access to facilities and expertise from three complementary disciplines at Kennedy Krieger Institute: Behavioral Psychology, Neuropsychology, and Motion Analysis. The scientists who utilize the Behavior Science Core work in various disciplines, but share a broad focus on research relevant to the effects of various factors that influence CNS development and functioning. In all of these studies, the objectives of the investigators are dependent on Behavior Science methods for objectively measuring specific aspects of performance or behavior. The Behavior Science Core supports these projects by guiding selection of appropriate measures, and training participants to cooperate with testing, assessment, and protocol-based intervention procedures. 

Behavior Science Core objectives are achieved through three phases:

1. Development and selection of appropriate methods
2. Pilot testing, redesign, refinement, and initial implementation by Core staff to demonstrate feasibility (when previous relevant experience is limited)
3. Training investigators' staff to implement the protocols and methods developed and incorporate them as a standard component of their research protocols

For projects in which the science has advanced to the point of testing interventions aimed at ameliorating the effects of CNS insult on development and functioning, participants often need training to cooperate with medical interventions (oral medication, respiratory support, pharmacotherapy, etc.). To ensure the success of these studies, the Behavior Science Core assists investigators with developing environmental and behavioral interventions to increase participant adherence to the medical protocol. Finally, in order to validate the benefits of the investigators' intervention protocols, repeated assessments with developmental, behavioral, neuropsychological, and/or movement measures must be conducted. The Behavior Science Core collaborates in selecting or developing these procedures, and in the analysis and interpretation of the resulting data.

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/clinical-translational-core

Keywords child development; developmental disorders; intellectual disabilities; genetic disabilities; acquired disabilities; clinical trials; translational research; biostatistics

Description

The overall objective of the Clinical Translational Core is to provide IDDRC-supported investigators with access to a broad range of supports of critical importance for the effective and efficient conduct of translational research focused on developmental disorders. Core resources are structured to coordinate those services of the Core, proper, and to ensure that the Core interacts seamlessly with complementary resources available in affiliated programs, including the Kennedy Krieger Institute's (KKI's) Clinical Trials Unit (CTU). This aim continues our Center's commitment to enhancing the conversion of basic science discoveries into effective therapies for children and adults with genetic and acquired developmental disabilities.

This Core is structured to complement our CTU, a program focused on the development of treatments targeting developmental disorders, including conducting investigational drug trials at all phases and supporting industry sponsorship of clinical trials. The Clinical Translational Core substantially expands upon CTU capabilities to provide expert resources including consultation on biostatistics and protocol design, pre-review prior to submission of protocols to the institutional review board (IRB) and hands-on advice and help with carrying out investigational protocols by experienced trialists, research coordinators and administrative staff.

To accomplish these goals, the Core provides IDDRC investigators with access to infrastructure and expertise focused on translation of basic science advances in the understanding of the pathogenesis of childhood neurodevelopmental disabilities into clinical trials of possible therapies for these disorders. This includes assistance with:

1. Recruitment of research participants through coordination with clinical programs, coordination of existing databases, development of new recruitment resources, and faculty participation in national registry development;
2. The conduct of clinical trials, facilitating access to the resources and expertise available within KKI's CTU;
3. Obtaining approvals from the IRB and the IACUC, as required;
4. Moving ideas and findings along the entire translational continuum and toward implementation in practice;
5. Accessing consultation and collaboration in the area of biostatistics;
6. Coordinating with other components of our IDDRC and with affiliated programs throughout Johns Hopkins involved in translational research.

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/genetics-core-objectives

Keywords Centralized tissue culture; amino acid analyses; organic acid analyses; molecular cytogenetics; cytogenetic analysis; karyotyping; genomic abnormalities; current-generation sequencing; molecular genetics; bioinformatics

Description

The Genetics Core supports research focused on the role genetic factors play in atypical physical, cognitive, and behavioral development. Supported research focuses on etiology, natural history, and prognosis of a variety of conditions associated with developmental delay, neuropsychiatric disorders affecting children, and behavioral and physical features of developmental disabilities. The services provided by the Genetics Core include:

• Cell line establishment and tissue culture
• Cytogenetic analysis, namely karyotype and fluorescence in situ hybridization
• Single nucleotide polymorphism microarray
• Identification of regions with genomic homozygosity and parent of origin for genomic abnormalities

The Core also serves as an interface for IDDRC-supported projects with the resources of other Genetics Core facilities established within the Johns Hopkins Medical Institutions, including current-generation sequencing.

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/neuroimaging-core

Keywords Magnetic resonance imaging; positron emission tomography; anatomic imaging; small animal imaging; developmental disabilities; intellectual disabilities; fMRI; proton magnetic resonance spectroscopy; trans-cranial magnetic stimulation

Description

The Neuroimaging Core provides assistance and guidance to investigators using various MRI paradigms in research studies relevant to developmental disorders. This assistance includes conceptualizing, planning, and implementing stimulus paradigms, MRI pulse sequences, and data analysis schema in order to optimize efficiency and to help investigators use available imaging technology. We also guide users of the Core to seek synergies across different types of imaging data (anatomic, functional, spectroscopic), and, when applicable, to incorporate trans-cranial magnetic stimulation techniques complementary to functional MRI.

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/research-project

Keywords child development; neurodevelopmental disorders; perinatal hypoxia-ischemia; mouse model; brain damage; therapeutic hypothermia; neuroprotection; nanotherapy; microglia; astrocytes; cerebral palsy

Description

Neurodevelopmental disorders such as cerebral palsy (CP) and autism are common chronic childhood disorders with no effective cure. Half a million children under the age of 18 in the US have CP, and an estimated 1 in 6 children have some form of developmental disability. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of CP and related disabilities. This project is focused on reducing brain damage and its associated morbidity and mortality risks in infants exposed to perinatal hypoxia-ischemia (HI), employing a mouse model to examine post-injury impacts of intervention.

Therapeutic hypothermia is an intervention known to reduce brain injury in term infants after perinatal asphyxia, but protection is typically incomplete and rates of mortality and severe disability remain high. Therapeutic hypothermia can also cause immune dysregulation and increase pro-inflammatory responses that are associated with worse outcomes. Moreover, rewarming may trigger seizures or increase glutathione consumption, leading to altered redox balance. Therefore, a critical need exists for complementary therapies that improve neuroprotection and address the negative effects of hypothermia and rewarming. This preclinical research project addresses this need by examining the effects of combining hypothermia with nanotherapeutic approaches for targeted delivery of drugs to injured neurons, activated microglia and reactive astrocytes in an established mouse model of HIE.  This work will lead to new strategies for targeted delivery of adjunct therapies for use with hypothermia, enabling sustained neuroprotection to reduce the incidence of neurodevelopmental disabilities, including CP, in neonates exposed to perinatal asphyxia.

URL: https://www.kennedykrieger.org/research-training/centers-labs-cores/intellectual-developmental-disabilities-research-center/translational-neuroscience-core

Keywords Synaptic neurochemistry; histology imaging; liquid chromatography; lipid biochemistry; general mass spectrometry; intellectual disabilities; developmental disabilities; preclinical model analysis; animal models; clinical trials; brain imaging; assays

Description

The Translational Neuroscience Core provides investigators with access to expertise in the analysis of preclinical (animal and human) models of developmental disorders and analysis of relevant clinical samples. Another primary goal of the Translational Neuroscience Core is to facilitate the transfer of basic discoveries to clinical trials. To achieve these objectives, the Core faculty includes scientists with expertise in modeling developmental disorders in animals, and experts who can perform assays that can unravel relevant biochemical/metabolic mechanisms that are not available elsewhere within the Hopkins community. Many of the investigators utilizing the Translational Neuroscience Core are interested in visualizing effects on the brain, and therefore the Core provides training and access to histology and preclinical imaging facilities. Another major function is to provide a group of highly specialized assays that target metabolites and molecules of relevance to intellectual and developmental disorders.