U01NS130588

Stroke Preclinical Assessment Network - Exploratory animal data on potential stroke therapies has not been predictive of clinical success. There are concerns over the design and conduct of pre-clinical studies, their reproducibility and generalizability.

The response to this challenge was the NINDS Stroke Preclinical Assessment Network (SPAN), an unbiased multicenter platform for preclinical confirmatory studies in translational stroke research. The MGH team was among the six laboratories selected by the peer review for this first iteration of SPAN (SPAN-1). We made major contributions to the design of SPAN-1.

MGH took charge of the MRI protocol for SPAN-1 and helped develop a fully automated analysis pipeline. We then contributed almost 400 animals in under 2 years to test six different acute stroke interventions. Each animal underwent two MRIs (days 2 and 30) and two neurological tests (days 7 and 28). Overall mortality was only ~10% during 28-day survival. Our technical losses amounted to just 17 animals. There were only 3 protocol deviations or violations.

Our overarching aim is to repeat this success in the next iteration of SPAN (SPAN-2). We are an experienced team of clinical and basic scientists capable of adjusting to the needs of the network. MGH SPAN team has collectively published over 100 manuscripts using various focal cerebral ischemia models and acute and chronic neurological outcome readouts in rodents.

MGH will also bring additional innovative approaches to SPAN-2, such as introducing MRI readouts for hemorrhagic transformation, blood-brain barrier (BBB) disruption, and tractography. We will complement the latter with optical imaging of resting state functional connectivity (RSFC) at the end of the follow-up period.

Aim 1. Contribute to SPAN-2 as a testing laboratory. We pledge to repeat our success in SPAN-1, working as a team with the rest of the network and sustaining our high standards with built-in redundancies to ensure our resilience in the face of personnel changes and disruptive events such as pandemics and weather.

Aim 2. Introduce innovative new structural and functional indices to enrich the SPAN readouts. We will go beyond recruiting subjects for the trial by introducing innovative readouts such as hemorrhage, edema, structural and functional connectivity, and histological analyses, which have not been part of SPAN-1.

Aim 3. Test whether an unbiased, multicenter, randomized, and blinded preclinical trial network can confirm or refute the published exploratory efficacy and safety data. We hypothesize that SPAN will have the statistical power and an unbiased structure to provide conclusive evidence confirming or refuting published exploratory data of prospective cerebroprotective therapies in ischemic stroke in combination with reperfusion.

For over a decade, we have advocated for and passionately supported the concept of an unbiased multicenter preclinical testing platform. We enthusiastically worked as part of SPAN-1 to ensure its success. And now we are fully committed to support SPAN-2 to make it a success as well.

The General Hospital Corporation

(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 NEUROSCIENCE WORKFORCE DEVELOPMENT, 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]

Charlestown, Massachusetts 02129 United States

Single Zip Code

Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection - Testing Laboratories (U01 Clinical Trial Not Allowed) (RFA-NS-22-003)

Amendment Since initial award the total obligations have increased 182% from $661,021 to $1,861,191.