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An Interneuron-based Cell Therapy for Epilepsy

Award Number: R01NS071785
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: 09/01/2010
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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An Interneuron-based Cell Therapy for Epilepsy - Project Summary/Abstract Cell transplantation, using GABAergic interneurons that integrate in host brain circuits, and function similar to endogenous inhibitory neurons could offer a novel therapeutic alternative for intractable epilepsies. Our work, over the past two decades, demonstrated that GABAergic progenitor cells derived from murine embryonic medial ganglionic eminence (MGE) integrate into host circuits (following transplantation in neonatal or adult mice), where they make functional inhibitory synapses, efficiently suppress epileptic seizure activity, and correct behavioral comorbidities associated with epilepsy. To establish an alternative source of MGE progenitor cells that would facilitate translation of this disease-modifying transplantation strategy to larger species, we recently established protocols using porcine embryonic MGE progenitor cells. Building on these findings, two specific aims are proposed: (i) to optimize intra-hippocampal xenotransplantation of porcine embryonic MGE progenitor cells and (ii) to evaluate the range of therapeutic benefits possible with porcine embryonic MGE progenitor cells. Techniques will involve cutting-edge electrophysiology, optogenetic and calcium imaging methods (in vitro and in vivo) to study functional integration of MGE-derived interneurons. Video-EEG monitoring, rodent epilepsy models, sophisticated behavioral assays, and confocal microscopy techniques will also be applied. Our results promise to provide new information about porcine MGE progenitors and direct demonstration(s) of the potential for xenotransplantation as a treatment for intractable epilepsies.


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 = $578,746 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	3/19/2025	NON-COMPETING CONTINUATION	$578,746
														Subtotal = $578,746

Issue Date FY: 2024 ( Subtotal = $624,741 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	4/11/2024	NON-COMPETING CONTINUATION	$45,084
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	3/18/2024	NON-COMPETING CONTINUATION	$579,657
														Subtotal = $624,741

Issue Date FY: 2023 ( Subtotal = $657,752 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	6/1/2023	NON-COMPETING CONTINUATION	$645,052
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/31/2023	COMPETING CONTINUATION	$12,700
														Subtotal = $657,752

Issue Date FY: 2022 ( Subtotal = $676,758 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/11/2022	COMPETING CONTINUATION	$676,758
														Subtotal = $676,758

Issue Date FY: 2014 ( Subtotal = $370,460 )
2014	2014	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/1/2014	NON-COMPETING CONTINUATION	$370,460
														Subtotal = $370,460

Issue Date FY: 2013 ( Subtotal = $361,107 )
2013	2013	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/24/2013	NON-COMPETING CONTINUATION	$361,107
														Subtotal = $361,107

Issue Date FY: 2012 ( Subtotal = $374,203 )
2012	2012	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/18/2012	NON-COMPETING CONTINUATION	$374,203
														Subtotal = $374,203

Issue Date FY: 2011 ( Subtotal = $374,199 )
2011	2011	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/26/2011	NON-COMPETING CONTINUATION	$350,387
2011	2011	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/25/2011	NON-COMPETING CONTINUATION	$23,812
														Subtotal = $374,199

Issue Date FY: 2010 ( Subtotal = $387,703 )
2010	2010	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/16/2010	NEW	$387,703
														Subtotal = $387,703

Grand Total All Awards = $4,405,669

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An Interneuron-based Cell Therapy for Epilepsy

Award Number: R01NS071785

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: 09/01/2010

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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