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Anti NMDA Receptor antibodes in adult brain dysfunction and fetal brain development: lessons from lupus

Award Number: P01AI073693
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PPG OVERALL Abstract: Neuropsychiatric lupus (NPSLE) is a common and debilitating manifestation of Systemic Lupus Erythematosus (SLE). For over a decade, we have been studying the contribution of a subset of anti-DNA antibodies that cross reacts with the N-methyl D-aspartate receptor, termed DNRAb, to cognitive impairment in NPSLE, and to impairments in fetal health of DNRAb+ mothers. We have developed a mouse model in which we have now shown that DNRAb, when they penetrate the hippocampus, cause acute neuronal death subsequently leading to persistent microglial activation, neuronal dendritic loss, and cognitive impairments. Suppression of microglial activation by angiotensin converting enzyme (ACE) inhibitors leads to a restoration of neuronal integrity and cognitive function. Using the same model, we have demonstrated that maternal DNRAb cause death of female fetuses and cognitive impairment in male offspring through transplacental transport. We have demonstrated in subjects with SLE that memory impairment is associated with increased titers of DNRAb and that a reduced microstructural integrity of parahippocampal fibers also associates with DNRAb. We proposed to continue to study both the mouse model and SLE patients, to understand the mechanisms of microglial activation and how ACE inhibitors restore neuronal integrity. We will determine how DNAbs alter male and female fetal brain development. We will assess microglial activation and loss of blood brain barrier integrity in SLE patients and the association of these abnormalities with elevated titers of DNRAb. These studies have already led to a funded clinical trial of ACE inhibitors in non-focal central nervous system manifestations of NPSLE, and have the potential to reveal additional potential therapeutic strategies.


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: 2024 ( Subtotal = $2,858,960 )
2024	2024	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	15	7/8/2024	NON-COMPETING CONTINUATION	$2,858,960
														Subtotal = $2,858,960

Issue Date FY: 2023 ( Subtotal = $3,039,860 )
2023	2023	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	14	7/10/2023	NON-COMPETING CONTINUATION	$3,039,860
														Subtotal = $3,039,860

Issue Date FY: 2022 ( Subtotal = $3,160,921 )
2022	2022	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	13	7/5/2022	NON-COMPETING CONTINUATION	$3,160,921
2022	2021	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	12	10/20/2021	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $3,160,921

Issue Date FY: 2021 ( Subtotal = $3,425,125 )
2021	2021	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	003	12	7/20/2021	NON-COMPETING CONTINUATION	$3,039,165
2021	2021	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	11	12/8/2020	SUPPLEMENT FOR EXPANSION	$196,504
2021	2021	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	004	12	8/16/2021	SUPPLEMENT FOR EXPANSION	$189,456
2021	2018	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	002	10	7/1/2021	NON-COMPETING CONTINUATION	$0
2021	2018	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	10	7/1/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,425,125

Issue Date FY: 2020 ( Subtotal = $2,883,980 )
2020	2020	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	11	7/10/2020	COMPETING CONTINUATION	$2,883,980
														Subtotal = $2,883,980

Issue Date FY: 2018 ( Subtotal = $2,672,219 )
2018	2018	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	10	9/6/2018	NON-COMPETING CONTINUATION	$413,610
2018	2018	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	10	6/26/2018	NON-COMPETING CONTINUATION	$2,258,609
														Subtotal = $2,672,219

Issue Date FY: 2017 ( Subtotal = $2,270,547 )
2017	2017	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	9	6/5/2017	NON-COMPETING CONTINUATION	$2,270,547
														Subtotal = $2,270,547

Issue Date FY: 2016 ( Subtotal = $2,270,547 )
2016	2016	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	8	6/13/2016	NON-COMPETING CONTINUATION	$2,270,547
														Subtotal = $2,270,547

Issue Date FY: 2015 ( Subtotal = $2,270,547 )
2015	2015	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	7	6/12/2015	NON-COMPETING CONTINUATION	$2,270,547
														Subtotal = $2,270,547

Issue Date FY: 2014 ( Subtotal = $2,287,670 )
2014	2014	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	6	7/2/2014	COMPETING CONTINUATION	$2,287,670
2014	2012	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	5	6/27/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,287,670

Issue Date FY: 2012 ( Subtotal = $2,221,830 )
2012	2012	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	5	7/31/2012	NON-COMPETING CONTINUATION	$2,221,830
														Subtotal = $2,221,830

Issue Date FY: 2011 ( Subtotal = $2,206,554 )
2011	2011	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	4	7/27/2011	NON-COMPETING CONTINUATION	$2,206,554
														Subtotal = $2,206,554

Issue Date FY: 2010 ( Subtotal = $2,229,232 )
2010	2010	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	3	8/3/2010	NON-COMPETING CONTINUATION	$2,229,232
2010	2009	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Trans-NIH Recovery Act Research Support	000	2	12/4/2009	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $2,229,232

Issue Date FY: 2009 ( Subtotal = $2,289,510 )
2009	2009	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	001	2	8/13/2009	NON-COMPETING CONTINUATION	$2,189,510
2009	2009	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Trans-NIH Recovery Act Research Support	002	2	8/28/2009	SUPPLEMENT FOR EXPANSION	$100,000
2009	2008	NORTH SHORE-LONG ISLAND JEWISH RESEARCH INSTITUTE	350 COMMUNITY DRIVE	MANHASSET	NY	11030	NASSAU	USA	Allergy and Infectious Diseases Research	000	1	2/27/2009	NEW	$0
														Subtotal = $2,289,510

Issue Date FY: 2008 ( Subtotal = $2,135,361 )
2008	2008	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Allergy and Infectious Diseases Research	000	1	7/29/2008	NEW	$2,135,361
														Subtotal = $2,135,361

Grand Total All Awards = $38,222,863

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Anti NMDA Receptor antibodes in adult brain dysfunction and fetal brain development: lessons from lupus

Award Number: P01AI073693

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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