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An optogenetic-based control paradigm for neuromodulation of bladder function following spinal cord injury

Award Number: R21EB031249
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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An optogenetic-based control paradigm for neuromodulation of bladder function following spinal cord injury - PROJECT SUMMARY More than 17,000 Americans suffer from spinal cord injuries every year, and many of these patients suffer from lower urinary tract dysfunction. One of these bladder disorders is detrusor-sphincter dyssynergia, where the detrusor muscle, which constricts to push urine out of the bladder, and the urethral sphincters, which relax to allow urine to pass out the urethra, cannot coordinate their actions to produce a void. Electrical neuromodulation technologies can be effective in improving symptoms of lower urinary tract dysfunction but due the complexity of the circuit and neural systems involved these therapies are unable to initiate a coordinated voiding contraction on-demand. To address these limitations, we plan to develop an optogenetic neuromodulatory approach to target and independently control the two main neuronal systems (parasympathetic and somatic motor) that are integral to the voiding reflex. Optogenetic neuromodulation involves genetically expressing optically activated proteins in neurons to modulate their activity with light stimulus. Using this method, we plan to express excitatory opsins in parasympathetic neurons innervating the detrusor by using promoter restricted expression and anatomically limited viral delivery (Aim 1). Activation of these neurons leads to detrusor/bladder contractions. To inhibit tonic urethral sphincter tone, we will use a similar approach to target the somatic motor neurons innervating the external urethral sphincter with inhibitory opsins (Aim 2). Inhibition of these neurons leads to sphincter relaxation. We will test the specificity of expression, potential off target effects, as well as the physiological effects of opsin activation in naïve and in a rat model of spinal cord injury. Finally, we will develop a control paradigm to coordinate activation of detrusor with urethral sphincter relaxation, to initiate coordinated and complete emptying of the bladder (Aim 3). The proposed project will develop innovative neuromodulatory techniques to control bladder function. Further development of refined and efficient neuromodulation techniques is the first step in developing closed-loop therapies to treat bladder dysfunction associated with spinal cord injury. Additionally, these techniques will have wide applicability in other fields of peripheral nervous system gene delivery and cell- type specific neuromodulation. Advances in neuromodulation of bladder function will bring us closer to goal of improving the lives of patients with spinal cord 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 = -$2,980 )
2025	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	2/10/2025	NON-COMPETING CONTINUATION	-$2,980
														Subtotal = -$2,980

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	4/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $190,625 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	1/24/2023	NON-COMPETING CONTINUATION	$19,062
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	12/21/2022	NON-COMPETING CONTINUATION	$171,563
														Subtotal = $190,625

Issue Date FY: 2022 ( Subtotal = $190,625 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	12/14/2021	NON-COMPETING CONTINUATION	$171,562
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	8/3/2022	NON-COMPETING CONTINUATION	$19,063
														Subtotal = $190,625

Issue Date FY: 2021 ( Subtotal = $228,750 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	3/10/2021	NEW	$228,750
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	6/3/2021	NEW	$0
														Subtotal = $228,750

Grand Total All Awards = $607,020

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An optogenetic-based control paradigm for neuromodulation of bladder function following spinal cord injury

Award Number: R21EB031249

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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