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Rewiring the Injured Brain with GABA Progenitors

Award Number: R01NS096012
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: 02/15/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Rewiring the Injured Brain with GABA Progenitors - Abstract Transplantation of neural progenitor cells has extraordinary potential for the treatment of many nervous system disorders. Several recent studies have shown that progenitor cells derived from the embryonic mouse medial ganglionic eminence (MGE) retain a unique ability to migrate and differentiate into GABAergic interneurons following transplantation into the juvenile or adult rodent brain. We recently demonstrated that these cells are effective in correcting memory impairments and preventing spontaneous seizures in a mouse model of traumatic brain injury. However, it is not known whether similar therapeutic effects can be achieved with clinically-relevant cell sources, such as human pluripotent stem cells. Here, we propose studies to evaluate the effect of human-derived interneurons in a pre-clinical model of traumatic brain injury. Our approach involves transplantation of human interneuron progenitors into a widely-used rodent model of closed-head injury at different stages following injury followed by in vitro patch-clamp recordings, immunofluorescence techniques and neural circuit mapping to evaluate the synaptic integration of grafted neurons. A battery of behavioral assays and video-EEG monitoring will also be applied. Two specific aims are proposed: (i) determine how human-derived GABA progenitors integrate into brain injured hippocampus, and (ii) test the therapeutic efficacy of human GABA neurons in a mouse model of traumatic brain injury. If successful, our results will help move these exciting technologies closer to the clinic by establishing relatively direct proof of concept for human interneuron transplantation to treat traumatic brain injury.


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 = $424,544 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	4/21/2025	NON-COMPETING CONTINUATION	$424,544
														Subtotal = $424,544

Issue Date FY: 2024 ( Subtotal = $420,540 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	7/22/2024	NON-COMPETING CONTINUATION	$420,540
														Subtotal = $420,540

Issue Date FY: 2023 ( Subtotal = $433,546 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	5/3/2023	NON-COMPETING CONTINUATION	$433,546
														Subtotal = $433,546

Issue Date FY: 2022 ( Subtotal = $433,546 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	5/9/2022	NON-COMPETING CONTINUATION	$433,546
														Subtotal = $433,546

Issue Date FY: 2021 ( Subtotal = $451,581 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	3/5/2021	COMPETING CONTINUATION	$451,581
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	8/22/2021	COMPETING CONTINUATION	$189,526
2021	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	8/22/2021	NON-COMPETING CONTINUATION	-$189,526
2021	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/5/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $451,581

Issue Date FY: 2020 ( Subtotal = $337,969 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/28/2020	NON-COMPETING CONTINUATION	$304,172
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/11/2020	NON-COMPETING CONTINUATION	$33,797
														Subtotal = $337,969

Issue Date FY: 2019 ( Subtotal = $337,969 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/23/2019	NON-COMPETING CONTINUATION	$337,969
														Subtotal = $337,969

Issue Date FY: 2018 ( Subtotal = $337,969 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/23/2018	NON-COMPETING CONTINUATION	$33,797
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/18/2018	NON-COMPETING CONTINUATION	$304,172
														Subtotal = $337,969

Issue Date FY: 2017 ( Subtotal = $337,969 )
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/30/2017	NON-COMPETING CONTINUATION	$33,797
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/18/2017	NON-COMPETING CONTINUATION	$304,172
														Subtotal = $337,969

Issue Date FY: 2016 ( Subtotal = $328,431 )
2016	2016	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/4/2016	NEW	$328,431
														Subtotal = $328,431

Grand Total All Awards = $3,844,064

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Rewiring the Injured Brain with GABA Progenitors

Award Number: R01NS096012

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: 02/15/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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