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Obesity as a Driver of Inflammation and Brain Volume Loss in Pediatric Multiple Sclerosis

Award Number: K23NS116225
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Obesity as a Driver of Inflammation and Brain Volume Loss in Pediatric Multiple Sclerosis - PROJECT SUMMARY/ABSTRACT Dr. Brenton is a pediatric neurologist whose long-term goal is to become an expert in multiple sclerosis (MS) therapeutics and risk factor modification. The training and mentored research experience proposed will enable him to develop expertise in: 1) the conduct of multi-centered clinical studies, 2) use of MRI as a research tool, and 3) obesity science. Dr. Brenton has assembled an expert team of mentors/advisors to help him. Dr. Karen Johnston (primary mentor) is a highly-successful international expert in clinical trial conduct, Dr. Myla Goldman (co-mentor) is a nationally-recognized expert in MS clinical research, and Dr. Brenda Banwell (co-mentor) is a world-expert in pediatric MS clinical research. Dr. Brenton will take courses pertinent to research methodology, the study of obesity and its relevant biomarkers, and the application of neuroimaging techniques in clinical research. He will also spend 5 weeks at the Children’s Hospital of Philadelphia to gain hands-on experience with Dr. Banwell in the use of neuroimaging as a biomarker for pediatric MS outcomes. Children with MS, the most common autoimmune disease of the central nervous system (CNS), experience failure of age-expected brain growth followed by progressive brain atrophy during adolescence. These children often develop physical and neurocognitive disability at a young age. Childhood obesity is an established risk determinant for pediatric MS, however, the impact of persisting obesity on MS disease course is unknown. In non-MS children and young adults, obesity (a national health epidemic) associates with progressive brain volume loss. In adults with MS, greater levels of obesity are associated with significantly reduced normalized gray matter volumes. This is important, as gray matter atrophy is directly linked with progressive disability in MS. The impact of obesity in children with MS has not been studied and the implications of this are particularly important in a pediatric patient – where the negative impact of obesity on the CNS may exert an even greater detrimental effect on a brain that is still undergoing development. We will conduct a cross-sectional, multi-center cohort study to determine the relationship between obesity and biomarkers of 1) inflammation (measured radiologically by T2-hyperintense inflammatory lesion volumes & serologically by adipocyte-derived cytokines) and 2) neurodegeneration (measured radiologically by whole brain volumetrics & serologically by neurofilament light chain). This study will help define the role of obesity in pediatric MS disease and will set the stage for future intervention studies aimed at modifiable risk factors in MS. Upon completion of this award, Dr. Brenton will be one of the only child neurologists in the world with formal training in pediatric MS in combination with training in obesity science and MS neuroimaging. His proposal represents the first and only prospective study evaluating the role of obesity on pediatric MS disease severity at presentation. This K23 will provide the necessary data and experience to inform future studies, and he will be well-poised to apply for future R01 funding as an independent, collaborative clinician-scientist.


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	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	10/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $187,423 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/15/2024	NON-COMPETING CONTINUATION	$187,423
														Subtotal = $187,423

Issue Date FY: 2024 ( Subtotal = $194,210 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/13/2023	NON-COMPETING CONTINUATION	$194,210
														Subtotal = $194,210

Issue Date FY: 2023 ( Subtotal = $192,301 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/9/2022	NON-COMPETING CONTINUATION	$192,301
														Subtotal = $192,301

Issue Date FY: 2022 ( Subtotal = $193,648 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/3/2021	NON-COMPETING CONTINUATION	$193,648
														Subtotal = $193,648

Issue Date FY: 2021 ( Subtotal = $194,292 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/23/2020	NEW	$194,292
														Subtotal = $194,292

Grand Total All Awards = $961,874

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Obesity as a Driver of Inflammation and Brain Volume Loss in Pediatric Multiple Sclerosis

Award Number: K23NS116225

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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