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Autoresuscitation and SUDEP

Award Number: R01NS126418
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Autoresuscitation and SUDEP - Project Summary Approximately 30% of people with epilepsy are refractory to current anti-seizure medications and sudden unexpected death in epilepsy (SUDEP) occurs in ~1:150 per year for individuals with severe refractory generalized convulsive seizures (GCS). The long-term goals of our research program are to identify novel molecular targets with disease-modifying effects that may increase longevity in those susceptible to SUDEP. Evidence from the multi- center MORTEMUS study on SUDEP indicates that patients experienced a series of events promoting hypoxic and hypercapnic (HH) fluctuations in blood gases, from which they were unable to autoresuscitate and succumbed to terminal apnea. However, the relationship between SUDEP risk and the efficacy of the autoresuscitation response is unknown. The objective of the proposed project is to elucidate mechanisms of autoresuscitation failure in relation to SUDEP risk. The central hypothesis is that alterations in the network of chemosensitive cardiorespiratory neurons increases the probability of autoresuscitation failure and SUDEP risk. Our rationale is that SUDEP is often associated with a preceding GCS, but demise has also been associated with prone positions with no evidence of seizure. A variable or decline in autoresuscitation efficacy may explain succumbing to one GCS and not previous seizures or failing to arouse in situations of changing air supply. Our specific aims will test the hypotheses that maladaptive modulatory control of key central autoresuscitation centers disintegrates the network chemoresponse, causing deterioration of the response and the autoresuscitation response to fail. Upon conclusion, we will have delineated mechanisms underlying autoresuscitation failure in the context of epilepsy in a clinically relevant animal model of SUDEP. This information will offer new research avenues for understanding SUDEP, assessing risk and identifying therapeutic opportunities.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $323,474 )
2025	2025	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/14/2025	NON-COMPETING CONTINUATION	$323,474
														Subtotal = $323,474

Issue Date FY: 2024 ( Subtotal = $347,896 )
2024	2024	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/10/2024	NON-COMPETING CONTINUATION	$322,790
2024	2024	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/6/2024	NON-COMPETING CONTINUATION	$25,106
														Subtotal = $347,896

Issue Date FY: 2023 ( Subtotal = $359,779 )
2023	2023	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/26/2023	NON-COMPETING CONTINUATION	$359,779
														Subtotal = $359,779

Issue Date FY: 2022 ( Subtotal = $359,375 )
2022	2022	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	5/10/2022	NEW	$51,854
2022	2022	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/29/2022	NEW	$307,521
														Subtotal = $359,375

Grand Total All Awards = $1,390,524

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Autoresuscitation and SUDEP

Award Number: R01NS126418

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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