Thursday, July 3, 2025 7/3/2025

Anti-CV2 autoantibodies unmask a CRMP5/GluN2B pain signaling hub

Award Number: R01NS119263
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: 05/14/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Anti-CV2 autoantibodies unmask a CRMP5/GluN2B pain signaling hub - Abstract Neuropathic pain is common neurological disorder affecting between 5-10% of the general population and predicted to become more common in the future because of the aging population. Although analgesics are available, this type of pain is particularly resistant to our current treatment strategies leaving patients with few options. In addition, these drugs cause severe side effects. This is of course hugely debilitating for individuals, negatively affecting their quality of life. Furthermore, it has significant economic ramifications (treatment costs, time spent off work) and is a burden on healthcare services that needs to be addressed. As a result, there is a pressing need to develop new better-targeted therapies for the treatment of neuropathic pain. One obstacle has been the lack of translation from basic science findings into the clinic. Here, we aim to address this by using patient samples to enhance the relevance of our basic research. It is now well accepted that neuroimmune interactions contribute to abnormal pain states and one relatively under studied aspect of is through the action of human autoantibodies. The anti-CV2 autoantibodies target a protein called collapsin response mediator protein 5 (CRMP5) and are associated with neuropathic pain in patients. CRMP5 is an understudied onconeural protein highly expressed in the developing brain. In adults, CRMP5 expression is absent from the brain but retained in sensory neurons, nerves and synapses present in the spinal cord. In neuropathic pain, CRMP5 expression is decreased at post-synaptic sites in the spinal cord, while the levels of GluN2B, a subunit of the NMDA receptor, and a novel CRMP5 binding protein, is increased. Using patients' autoantibodies and a rat model of neuropathic pain, we will test the hypothesis that disruption of CRMP5 functions underlies allodynia in anti-CV2 autoimmune neuropathy and in neuropathic pain. Aim 1 will investigate the alterations of sensory neurotransmission elicited by anti-CV2 autoantibodies. This will include a functional profiling of sensory neurons using whole cell and slice electrophysiology. With this we will decipher the site of action of anti-CV2 autoantibodies produce to allodynia. Aim 2 will focus on elucidating the pre- and post-synaptic function of CRMP5 in spinal neurotransmission and neuropathic pain. We will explore the novel idea that loss of CRMP5 regulation of GluN2B underlies allodynia in neuropathic pain. This proposal uses a combination of novel biochemical and functional methods to reverse-translate the clinical findings of CRMP5 (anti-CV2) auto-immunity causing allodynia to interrogate how CRMP5 can contribute to neuropathic pain. The identification of a novel therapeutic target for chronic pain is an exciting outcome with far reaching applications for future therapeutic development.


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 = $351,855 )
2025	2025	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/15/2025	NON-COMPETING CONTINUATION	$351,855
														Subtotal = $351,855

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/26/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $729,541 )
2023	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/21/2022	NON-COMPETING CONTINUATION	$316,669
2023	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	5/10/2023	SUPPLEMENT FOR EXPANSION	$377,686
2023	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	5/18/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/1/2023	NON-COMPETING CONTINUATION	$35,186
2023	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	3	6/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$38,938
2023	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	2	6/8/2023	NON-COMPETING CONTINUATION	-$35,649
2023	2021	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	1	6/8/2023	NEW	-$3,289
														Subtotal = $729,541

Issue Date FY: 2022 ( Subtotal = $356,499 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	8/4/2022	NON-COMPETING CONTINUATION	-$320,850
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/6/2022	NON-COMPETING CONTINUATION	$35,649
2022	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	8/4/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$320,850
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/20/2022	NON-COMPETING CONTINUATION	$320,850
														Subtotal = $356,499

Issue Date FY: 2021 ( Subtotal = $368,934 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	1/25/2021	NEW	$0
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/24/2020	NEW	$368,934
														Subtotal = $368,934

Grand Total All Awards = $1,806,829

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Anti-CV2 autoantibodies unmask a CRMP5/GluN2B pain signaling hub

Award Number: R01NS119263

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: 05/14/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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