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Multipronged approach to promote functional axonal regeneration in the spinal cord after injury

Award Number: R01NS085426
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Multipronged approach to promote functional axonal regeneration in the spinal cord after injury - PROJECT SUMMARY The lack of successful regeneration after injury in the mature central nervous system is due to intrinsic and environmental obstacles. Though progress in the field has been made, overcoming these barriers to result in robust functional axon regeneration and recovery is still a significant challenge. We build upon preliminary data and hypothesize that recurrent DREADD-mediated neuronal activation after injury is a means to enhance functional axon regeneration. Additionally, we will test the hypothesis that neuronal activation increases axon regeneration via both mTOR activation and increasing dynamic microtubules. We will these our hypotheses both in vitro using adult dorsal root ganglion neuron cultures and in vivo using dorsal root crush, dorsal columns spinal cord injury (SCI)/peripheral nerve graft (PNG), and incomplete cervical SCI/PNG models. In Aim 1, we will elucidate how repeated, chemogenetic neuronal activation enhances axon regeneration. In Aim 2, we will assess if neuronal activation – alone or in combination with manipulations that increase dynamic microtubules and mTOR activation – promotes functional axon regeneration. Collectively, we will: 1) elucidate mechanisms behind how neuronal activation enhances growth, potentially identifying new therapeutic targets; 2) determine the extent to which neuronal activation enhances regeneration in different injury models (dorsal root crush, SCI); 3) determine if neuronal activation has disparate or similar effects in different populations of neurons (DRG vs. CNS); 4) test whether meaningful axonal regeneration is facilitated using a unique, multi-faceted approach that: a) uses chemogenetic neuronal activation – possibly along with further increasing dynamic microtubules and/or mTOR activation – to enhance the axonal growth response; b) provides a more growth-permissive environment after an injury (i.e. mitigation of the inhibitory matrix of the glial scar with chondroitinase; transplantation of a PNG into an SCI cavity; chondroitinase digestion of plasticity-limiting perineuronal nets). After the completion of these experiments, we will have identified novel therapeutic avenues to foster functional repair after SCI.


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 = $361,423 )
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	3/12/2024	NON-COMPETING CONTINUATION	-$73,098
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	10	7/26/2024	NON-COMPETING CONTINUATION	$23,199
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	2/15/2024	NON-COMPETING CONTINUATION	$371,364
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	2/19/2024	SUPPLEMENT FOR EXPANSION	$39,958
														Subtotal = $361,423

Issue Date FY: 2023 ( Subtotal = $409,744 )
2023	2023	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	2/7/2023	SUPPLEMENT FOR EXPANSION	$78,338
2023	2023	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/28/2023	NON-COMPETING CONTINUATION	$331,406
														Subtotal = $409,744

Issue Date FY: 2022 ( Subtotal = $409,744 )
2022	2022	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	1/28/2022	SUPPLEMENT FOR EXPANSION	$78,338
2022	2022	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	3/30/2022	NON-COMPETING CONTINUATION	$33,141
2022	2022	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/20/2022	NON-COMPETING CONTINUATION	$298,265
														Subtotal = $409,744

Issue Date FY: 2021 ( Subtotal = $330,859 )
2021	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	2/5/2021	NON-COMPETING CONTINUATION	$33,087
2021	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	12/23/2020	NON-COMPETING CONTINUATION	$297,772
														Subtotal = $330,859

Issue Date FY: 2020 ( Subtotal = $336,328 )
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	7/8/2020	COMPETING CONTINUATION	$632
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	12/20/2019	COMPETING CONTINUATION	$336,328
2020	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/19/2019	NON-COMPETING CONTINUATION	$0
2020	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	7/8/2020	NON-COMPETING CONTINUATION	-$632
														Subtotal = $336,328

Issue Date FY: 2018 ( Subtotal = $337,969 )
2018	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/16/2018	NON-COMPETING CONTINUATION	$304,172
2018	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/8/2018	NON-COMPETING CONTINUATION	$33,797
														Subtotal = $337,969

Issue Date FY: 2017 ( Subtotal = $337,969 )
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/19/2017	NON-COMPETING CONTINUATION	$304,172
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/31/2017	NON-COMPETING CONTINUATION	$33,797
														Subtotal = $337,969

Issue Date FY: 2016 ( Subtotal = $337,969 )
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/17/2016	NON-COMPETING CONTINUATION	$337,969
														Subtotal = $337,969

Issue Date FY: 2015 ( Subtotal = $387,683 )
2015	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/10/2015	SUPPLEMENT FOR EXPANSION	$49,714
2015	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/20/2015	NON-COMPETING CONTINUATION	$337,969
														Subtotal = $387,683

Issue Date FY: 2014 ( Subtotal = $337,969 )
2014	2014	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/3/2014	NEW	$337,969
														Subtotal = $337,969

Grand Total All Awards = $3,587,657

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Multipronged approach to promote functional axonal regeneration in the spinal cord after injury

Award Number: R01NS085426

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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