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Potentiate Cav3.3 To Treat Cognitive Deficits Associated with Impaired Sleep Spindle

Award Number: R01MH131719
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Potentiate Cav3.3 To Treat Cognitive Deficits Associated with Impaired Sleep Spindle - Project Summary/Abstract Sleep spindle is a hallmark brain oscillation occurring in NREM (non-rapid eye movement) sleep that reflect intrinsic thalamocortical offline processing. Spindles are waxing and waning bursts of 12-15 Hz oscillations that originate in Thalamic Reticular Nucleus (TRN) when its neurons undergo bursting firing, and TRN- Thalamic Relay network oscillates at spindle frequency through the reciprocal connection. Sleep spindles are markedly reduced in schizophrenia patients as well as in Alzheimer patients, two very different CNS disorders yet both demonstrated significant altered sleep spindle properties associated with cognitive impairment. We hypothesize that hypofunctional TRN may underlie the risk/symptoms of these two devasting illnesses. CACNA1I is encode the α1 functional core of the CaV3.3 voltage-ˇgated calcium channels, and its expression is enriched in TRN. We have discovered two novel chemical scaffolds that potentiate CaV3.3 function, and this proposal aims to deliver in vivo ready Cav3.3 positive modulators. This multidisciplinary effort is expected to yield a panel of incisive pharmacological reagents to enhance CaV3.3 function in the brain and nominate candidates for preclinical development for treating cognitive impairments in schizophrenia patients.


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: 2026 ( Subtotal = $0 )
2026	2023	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	2	12/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	001	2	8/15/2025	NON-COMPETING CONTINUATION	$0
2025	2023	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	2	11/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	2	6/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,119,135 )
2023	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	1	5/30/2023	SUPPLEMENT FOR EXPANSION	$389,972
2023	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	001	2	6/28/2023	NON-COMPETING CONTINUATION	$729,163
														Subtotal = $1,119,135

Issue Date FY: 2022 ( Subtotal = $716,980 )
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	001	1	9/7/2022	NEW	$0
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	1	8/31/2022	NEW	$716,980
														Subtotal = $716,980

Grand Total All Awards = $1,836,115

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Potentiate Cav3.3 To Treat Cognitive Deficits Associated with Impaired Sleep Spindle

Award Number: R01MH131719

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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