R01NS124051

NSR-GENE (Neonatal Seizure Registry, Genetics of Post-Neonatal Epilepsy) - Project Summary

Neonatal seizures due to brain injury (acute symptomatic seizures) are associated with a high risk of post-neonatal epilepsy. Although clinical risk factors can help predict which children are at the highest risk for epilepsy, little is known about how genetic factors modify the risk for epilepsy after acute symptomatic neonatal seizures.

The proposed "Neonatal Seizure Registry - Genetics of Epilepsy (NSR-GENE)" study will test the central hypothesis that children who develop post-neonatal epilepsy are more likely to have pathogenic variants in epilepsy genes. Additionally, there may be an enrichment in single nucleotide polymorphisms within key inflammatory, neurotransmitter transport and homeostasis, and neurotrophic gene pathways compared to children who do not develop unprovoked seizures before the age of five years. These genetic factors can potentially be added to traditional clinical risk factors to predict epilepsy after neonatal seizures.

This observational study leverages the infrastructure of the nine-center Neonatal Seizure Registry, which has already recruited over 300 children with acute symptomatic neonatal seizures (NCT02789176, NCT04337697). This unique cohort of children and their parents will be invited to participate in non-invasive genetic testing. By utilizing neonatal clinical, EEG, and MRI measures available through the registry, along with genetic testing results, robust models will be built to predict the risk of epilepsy and elucidate mechanisms of epileptogenesis.

The study aims to pursue the following specific objectives:

AIM 1: Determine whether there is an increased incidence of pathogenic coding single nucleotide variants (SNVs) and gene-rich copy number variants (CNVs) within epilepsy genes among children with acute provoked neonatal seizures and post-neonatal epilepsy compared to those without subsequent epilepsy.

AIM 2: Determine whether an increased incidence of non-coding single nucleotide polymorphisms (SNPs) with a priori linkage to epilepsy is associated with the risk of post-neonatal epilepsy.

AIM 3: Develop prediction rules to stratify neonates based on the risk for post-neonatal epilepsy.

This innovative proposal will maintain an existing multicenter cohort enrolled from US centers that employ state-of-the-art technology for the diagnosis and investigation of neonatal seizures. It specifically targets the research priorities of parents and clinicians. The carefully designed study will provide novel, clinically relevant answers to key questions about epilepsy in this highly vulnerable patient population. The results will inform the subsequent design of intervention studies and programs aimed at reducing the risk of epilepsy after early-life seizures.

San Francisco Regents Of The University Of California

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM; RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS; RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS; IMPROVED METHODS OF DISEASE PREVENTION; NEW METHODS OF DIAGNOSIS AND TREATMENT; DRUG DEVELOPMENT; DEVELOPMENT OF NEURAL DEVICES; CLINICAL TRIALS; AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH; SYNAPSE FORMATION, FUNCTION, AND PLASTICITY; LEARNING AND MEMORY; CHANNELS, TRANSPORTERS, AND PUMPS; CIRCUIT FORMATION AND MODULATION; BEHAVIORAL AND COGNITIVE NEUROSCIENCE; SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION; NEUROENDOCRINE SYSTEMS; SLEEP AND CIRCADIAN RHYTHMS; AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE; TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM; NEURODEGENERATIVE DISORDERS; MOVEMENT DISORDERS; BRAIN TUMORS; CONVULSIVE DISORDERS; INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM; IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS; DISORDERS RELATED TO SLEEP; AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE THE NEUROSCIENCE WORKFORCE, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM; TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

San Francisco, California 94143 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 332% from $772,037 to $3,333,019.