The Mindich Child Health and Development Institute develops initiatives to further its mission of facilitating translational research of diseases affecting infants, children, and adolescents.
Pediatric Precision Medicine Initiative
The Mindich Child Health and Development Institute (MCHDI) is proud to announce the launch of the Mount Sinai Pediatric Precision Medicine Initiative. At Mount Sinai, the strong commitment to developing scientific infrastructure for genomic technology and precision medicine has positioned our institution to lead the nation in applying state-of-the-art genomic research methodology to advancing patient care. This new initiative will bring together Mount Sinai care providers and investigators with diverse expertise throughout the Departments of Pediatrics and Genetics and Genomic Sciences, as well as the Icahn Institute for Genomics and Multiscale Biology, the Charles Bronfman Institute for Personalized Medicine, and the Precision Immunology Institute.
Precision medicine (PM) uses individualized patient data to accurately and rapidly diagnose disease, better predict the outcomes of medical issues, and treat illnesses more precisely and effectively. Currently, medical problems with strong genetic underpinnings such as birth defects, neurodevelopmental delays, and inborn errors of immunity are ones that typically manifest during infancy, childhood and/or adolescence, and where a PM approach can be transformative. Moreover, these types of conditions can lead to diagnostic odysseys, during which young patients are subjected to extensive medical testing for months or years, families wait anxiously for definitive answers, and effective therapies, when available, are delayed. Through the MCHDI’s exciting new Pediatric Precision Medicine Initiative, we will improve outcomes by applying state-of-the-art genomic technologies as early as possible in the course of a child’s disorder.
Recent advances in genomic medicine have enabled the PM approach that we will undertake. Using just a few drops of blood from the child, we are able to perform high-capacity DNA sequencing to examine the genes that provide instructions for all of the body’s proteins. Especially when compared to similar sequencing of the patient’s parents in order to identify the rare differences, our ability to pinpoint disease-causing DNA mutations is unparalleled in medical history. To date, our experiences have proven that this approach can solve medical mysteries, identifying known disease genes presenting in unexpected ways as well as allowing us to pinpoint novel ones.
We are offering this PM approach to infants, children, and teenagers with some of the most complex and difficult-to-diagnose medical issues. In addition to accelerating and improving their care, this program will advance medical education by preparing the young physicians in pediatric training at Mount Sinai to use genomic medicine effectively, allowing them to better serve the community in their future practices.
Pediatric Clinical Trials Office
Clinical Trials are the final step that is required to prove that a therapeutic method can work in humans. Most such trials are done in adults, but the results of trials in adults are not necessarily entirely applicable to children. Pediatric clinical trials are therefore required to evaluate the efficacy of therapeutic or diagnostic strategies in pediatric populations, and the conduct of such trials has long been recognized as a priority by regulatory and funding agencies. However, conducting clinical trials in children necessitate specific approaches to study design and conduct that require special expertise. For example: the approach to consent is different (consent is required from the parents, and an assent, which is not a full consent, is required of children – depending on the age and cognitive ability), study design and processes may be quite different in different developmental stages, medication doses are calculated per patient/ patient characteristics (e.g., body mass index) rather than kept as a constant, and so on. It is furthermore recognized that patient recruitment to pediatric trials could be more complicated and that because pediatric diseases are generally less common, trials are likely to involve multisite designs.
For those reasons, MCHDI leadership decided to create a clinical trials program that will serve the needs of researchers within the Mount Sinai health system who wish to conduct pediatric clinical trials. The program will offer expertise in regulatory, budgeting, and operations of trials that involve children and families. We have partnered with the Clinical Trials Office (CTO) in Internal Medicine to provide this unique service which would offer its services to existing and “in development” trials, whether they involve investigator-initiated, industry-funded, or federally funded efforts. Under the support and supervision of the CTO Director, MCHDI leadership, and a dedicated group of pediatric investigators who are already successfully engaged in clinical trials research, a program manager will be charged with creating an operational team that will provide knowledgeable, efficient and convenient support to our diverse initiatives (which have been run in separate silos up until now).
Our vision is to enhance and expand current efforts, allow the development of future ideas and initiatives, reduce the startup costs and time-to-implementation of novel therapeutics, while promoting a collaborative multidisciplinary research enterprise in order to improve the health and quality of life of children.
Center for Inborn Errors of Immunity
Inborn errors of immunity comprise over 400 different monogenic disorders. These disorders present in various clinical features: infection (life-threatening or recurrent), malignancy, autoinflammation, autoimmunity or severe allergy. Most of these conditions manifest in childhood– although some can first manifest in adulthood. Inborn errors of immunity carry important morbidity and mortality, and are a significant burden to health economics systems. Moreover, uncovering the genetic diagnosis in an early stage of the disease is crucial for designing the optimal treatment, be it a drastic measure (hematopoietic stem cell transplantation or gene therapy), a therapy targeted to the cellular pathway that is defective, or a generic treatment with antibiotics/immunoglobulins to prevent irreversible end-organ damage.
As such, this Center has found an excellent niche within the MCHDI: The Center is truly a “bed to bench and back” program. Hence, the Center for Inborn Errors of Immunity program aims to embrace all physicians, physician-scientists, and scientists working on the immune system and the organ systems affected by a defect in the immune system. This broad research effort encompassing genomic strategies as well as classic molecular immunology aims to unravel the pathophysiology of known but poorly described inborn errors of immunity and to decipher new inborn errors of immunity. Most importantly, we aim to identify and develop new tools for precision therapy in children and adults affected by inborn errors of immunity. The Center is co-sponsored by the MCHDI and Precision Immunology Institute.
Functional Genomics and Disease Modeling Core
This core studies rare Mendelian and genetic diseases and is co-sponsored by the MCHDI and the Department of Cell, Developmental & Regenerative Biology. By using Drosophila disease models, it provides an integrated cellular signaling analysis, high-throughput whole animal drug screens, and functional genomic modifier analysis, aiming to better understand disease and identify therapeutics. This functional genomics approach aims to integrate mechanism-based understandings of disease with existing and novel therapeutics.