Increased understanding of the developing brain and how deviations from normal development can increase the risk of neurological and psychiatric diseases has created a rich landscape of opportunity for collaborations between leading academic medical centers and pharmaceutical and biotechnology companies dedicated to identifying new drugs and other interventions to help children.
We understand that successful collaborations depend upon a common understanding of goals and a shared commitment to milestone-driven progress. Thus, to support and enhance our collaborations with industry partners dedicated to improving the lives of children with nervous system disorders, the Translational Neuroscience Center (TNC) at Boston Children’s Hospital has recruited Robin Kleiman, PhD, as the head of preclinical research. Dr. Kleiman is a neurobiologist with more than a decade of drug discovery experience. She is available to discuss common interests, resource needs and a variety of collaborative approaches with prospective industry partners. Topics of special interest include:
- Target identification and validation, particularly in the areas of:
- Neurodevelopmental disorders
- Pain and regeneration
- Musculoskeletal disorders
- Identification of novel therapeutic molecules using cell-based screens
- IPSC derived neuron models of disease for genetically defined patient populations
- Additional therapeutic applications for molecules in clinical development
- Competitive differentiation for existing molecules
- Biomarker discovery
- Launching industry-sponsored trials at Boston Children’s with experienced regulatory staff
- Phase 0 studies (biomarker studies/target engagement/patient stratification):
- Integrated clinical EEG measures and interpretation
- Clinical imaging: PET, fMRI, MRI with diffusion tensor imaging
- Expertise across behavioral/cognitive scales and development of novel fit-for-purpose behavioral/cognitive batteries
- Phase 1 studies (safety and pharmacokinetics)
- Phase 2 studies (proof-of-concept)
- Large populations of patients with genetically defined conditions
Examples of Patient Populations Followed at Boston Children’s Hospital
Target Identification and Validation: The focus of basic neuroscience research at Boston Children’s Hospital encompasses genetic-molecular research and systems-circuits-behavior research to advance understanding of the developing brain. Our research leverages the interdisciplinary expertise of TNC faculty and the rich phenotypic data collected across multiple platforms from our global patient population. Our goal is to identify novel therapeutic targets and participate in both preclinical and clinical studies of new drugs and other interventions. A unique strength of the TNC is our ability to study analogous phenotypes in rare genetic populations and the corresponding genetic animal models of disease.
Identification of new therapeutic applications for known drugs: Boston Children’s investigators have developed and characterized a wide variety of preclinical assays and animal models useful for identifying additional therapeutic indications for safe compounds. In our core facilities, we can profile models using behavioral, electrophysiological and image-based endpoints.
A sample of mouse models available at Boston Children’s include:
- Rett syndrome
- Spinal muscular atrophy
- Tuberous sclerosis
- MDX model of Duchenne muscular dystrophy
- Fragile X Syndrome
- Shank3 and Cntnap2 models displaying autistic-like features
Competitive Differentiation: Our clinician researchers have extensive, real-world experience with therapeutic standards of care across a wide range of diseases and can offer unique perspectives on the relative strengths and shortcomings of current therapies. Our basic scientists can provide novel insights into disease mechanisms, leading to new avenues for exploring undesirable side effects or for demonstrating additional dimensions of efficacy. Consultations with the TNC faculty in our collaborative environment provide a foundation for customized experimental designs to speed the development of new drugs for pediatric neurological diseases.
Biomarker Discovery: The Translational Neuroscience Center at Boston Children’s Hospital has access to world-class facilities for biomarker development and state-of-the-art brain imaging.