Sunday, August 17, 2025 8/17/2025

Painful Versus Insensate Diabetic Neuropathy

Award Number: R01NS043314
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: 01/01/2003
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Painful Versus Insensate Diabetic Neuropathy - Project Summary Patients with prediabetes and diabetes are at an elevated risk for diabetic peripheral neuropathy (DPN). DPN primarily affects the distal limbs and is associated with pain, loss of sensation, gait abnormalities and reduced quality of life. This renewal will focus on a dietary intervention using a ketogenic diet (KD) to prevent and reverse symptoms of DPN. Consumption of a KD results in elevated ketone bodies, with beta- hydroxybutyrate (bOHB) and acetoacetate as key mediators. Generated by the liver, ketone bodies can be used directly by non-hepatic cells, such as neurons, as an alternative fuel source to glucose or in a signaling capacity. Axon degeneration in DPN, particularly small fibers, leads to reduced epidermal innervation for which there are currently no clinical treatments. The metabolic and energetic status of sensory axons contributes to axon loss, and the addition of ketone bodies as a fuel source could be an important modulator of cellular energy and metabolic function. Pain is a major contributor to decreased quality of life in patients with DPN, which is compromised by a lack of effective clinical treatments. Our overall hypothesis is that ketone bodies improve features of DPN through actions directly on sensory neurons. We will test our hypothesis using dietary interventions in mouse models of prediabetes and diabetes, as well as incorporate a Cre-lox mouse model lacking the ability to utilize ketone bodies in sensory neurons (advCre-SCOT-/- mice) to determine whether direct effects of ketones on peripheral sensory neurons drive these beneficial effects. Aim 1 will test whether ketone bodies act directly on sensory neurons to stimulate axon growth in DPN. Experiments will include both in vitro and in vivo assessment of axon growth as a result of a KD, and explore cellular signaling pathways involved in axon guidance, energy signaling pathways, and mitochondrial function. Aim 2 will test whether ketone bodies reduce pain (mechanical allodynia) in DPN by scavenging MGO. Experiments will incorporate ex vivo electrophysiology to identify response and firing properties of identified sensory neurons in settings of MGO and a KD. Additional experiments will test whether a KD has similar anti-nociceptive action in a chemotherapy- induced neuropathy model where changes in metabolism do not play a role. Results from these studies will fill an important gap in DPN research by providing new information about how a KD can improve neuronal metabolism and stimulate axon growth. These results will identify interventions that could be developed for pain control in DPN, including new mechanisms related to MGO toxicity.


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 = $332,213 )
2025	2025	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	2/13/2025	NON-COMPETING CONTINUATION	$332,213
														Subtotal = $332,213

Issue Date FY: 2024 ( Subtotal = $358,050 )
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	18	8/15/2024	NON-COMPETING CONTINUATION	-$11,074
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	5/3/2024	NON-COMPETING CONTINUATION	$36,911
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	1/23/2024	NON-COMPETING CONTINUATION	$332,213
														Subtotal = $358,050

Issue Date FY: 2023 ( Subtotal = $369,124 )
2023	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	4/25/2023	NON-COMPETING CONTINUATION	$369,124
														Subtotal = $369,124

Issue Date FY: 2022 ( Subtotal = $404,337 )
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	16	7/12/2022	COMPETING CONTINUATION	$24,944
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	1/31/2022	COMPETING CONTINUATION	$404,337
2022	2019	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	1/25/2022	NON-COMPETING CONTINUATION	$0
2022	2019	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	15	7/12/2022	NON-COMPETING CONTINUATION	-$24,944
														Subtotal = $404,337

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	5/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $330,313 )
2019	2019	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	5/28/2019	NON-COMPETING CONTINUATION	$330,313
														Subtotal = $330,313

Issue Date FY: 2018 ( Subtotal = $330,313 )
2018	2018	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	5/17/2018	NON-COMPETING CONTINUATION	$330,313
														Subtotal = $330,313

Issue Date FY: 2017 ( Subtotal = $330,313 )
2017	2017	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	5/26/2017	NON-COMPETING CONTINUATION	$33,032
2017	2017	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/15/2017	NON-COMPETING CONTINUATION	$297,281
														Subtotal = $330,313

Issue Date FY: 2016 ( Subtotal = $330,313 )
2016	2016	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	7/14/2016	NON-COMPETING CONTINUATION	$330,313
														Subtotal = $330,313

Issue Date FY: 2015 ( Subtotal = $330,313 )
2015	2015	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	7/27/2015	COMPETING CONTINUATION	$330,313
2015	2013	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	7/24/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $330,313

Issue Date FY: 2013 ( Subtotal = $310,308 )
2013	2013	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	8/2/2013	NON-COMPETING CONTINUATION	$310,308
														Subtotal = $310,308

Issue Date FY: 2012 ( Subtotal = $321,563 )
2012	2012	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	8/22/2012	NON-COMPETING CONTINUATION	$321,563
														Subtotal = $321,563

Issue Date FY: 2011 ( Subtotal = $321,563 )
2011	2011	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	8/18/2011	NON-COMPETING CONTINUATION	$321,563
														Subtotal = $321,563

Issue Date FY: 2010 ( Subtotal = $324,845 )
2010	2010	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	8/5/2010	NON-COMPETING CONTINUATION	$324,845
														Subtotal = $324,845

Issue Date FY: 2009 ( Subtotal = $328,125 )
2009	2009	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	8/31/2009	COMPETING CONTINUATION	$328,125
														Subtotal = $328,125

Issue Date FY: 2007 ( Subtotal = $299,281 )
2007	2007	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/19/2007	NON-COMPETING CONTINUATION	$299,281
														Subtotal = $299,281

Issue Date FY: 2006 ( Subtotal = $308,220 )
2006	2006	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/1/2005	NON-COMPETING CONTINUATION	$308,220
														Subtotal = $308,220

Issue Date FY: 2005 ( Subtotal = $315,638 )
2005	2005	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/11/2005	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$315,638
														Subtotal = $315,638

Issue Date FY: 2004 ( Subtotal = $315,638 )
2004	2004	UNIVERSITY OF KANSAS, MEDICAL CENTER	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/22/2003	NON-COMPETING CONTINUATION	$315,638
														Subtotal = $315,638

Issue Date FY: 2003 ( Subtotal = $327,750 )
2003	2003	UNIVERSITY OF KANSAS, MEDICAL CENTER	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1		NEW	$327,750
														Subtotal = $327,750

Grand Total All Awards = $6,288,220

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Painful Versus Insensate Diabetic Neuropathy

Award Number: R01NS043314

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: 01/01/2003

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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