Wednesday, August 20, 2025 8/20/2025

Mechanisms of Motor Neuron Injury in Acute Flaccid Myelitis

Award Number: K08NS124989
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Mechanisms of Motor Neuron Injury in Acute Flaccid Myelitis - Project Summary/Abstract Mechanisms of Motor Neuron Injury in Acute Flaccid Myelitis Acute flaccid myelitis (AFM) is an infectious disorder of motor neurons that resembles poliomyelitis. AFM predominantly affects children and has tragic consequences, often leading to lifelong paralysis. Concerningly, the incidence of AFM has increased exponentially with each recent outbreak. Effective treatment options for AFM are lacking, owing primarily to our poor understanding of disease pathogenesis. In the proposed work, I will investigate mechanisms of motor neuron toxicity in AFM. The majority of cases of AFM are caused by Enterovirus D68 (EV68). Therefore, I will focus on the infection of motor neurons by EV68 as a model of AFM. First, I will evaluate the role of nucleocytoplasmic transport in motor neuron toxicity following EV68 infection. This pathway is known to be altered in enterovirus infection and is also a key determinant of motor neuron toxicity in neurodegenerative disease. I will further define the mechanism of disruption of the nuclear pore complex by EV68, its effects on nucleocytoplasmic transport and motor neuron toxicity, and whether it can be pharmacologically targeted to prevent motor neuron death in vitro. Second, to better define the pathologic cascade following EV68 infection, I will investigate early pathologic events in a novel co-culture system including motor neurons and muscle fibers. I will specifically investigate changes in motor neuron morphology, electrophysiologic activity, and neuromuscular junction integrity. Third, I will determine whether host genetic background influences EV68 infectivity or subsequent motor neuron toxicity by studying iPS motor neurons derived from AFM patients compared to unrelated controls. Collectively, these studies will advance our understanding of pathogenic mechanisms in EV68-associated AFM and evaluate putative therapeutic targets. The experiments will also develop and refine model systems for the study of AFM and generate important preliminary data for future studies leading to scientific independence. The training plan will provide new training in virology methods and extend my expertise in iPS-based neurologic disease modeling and advanced microscopy.


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 = $234,360 )
2025	2025	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/24/2025	NON-COMPETING CONTINUATION	$234,360
														Subtotal = $234,360

Issue Date FY: 2024 ( Subtotal = $234,360 )
2024	2024	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/27/2024	NON-COMPETING CONTINUATION	$234,360
														Subtotal = $234,360

Issue Date FY: 2023 ( Subtotal = $234,360 )
2023	2023	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/23/2023	NON-COMPETING CONTINUATION	$234,360
														Subtotal = $234,360

Issue Date FY: 2022 ( Subtotal = $234,360 )
2022	2022	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	8/11/2022	NEW	$35,856
2022	2022	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/28/2022	NEW	$198,504
														Subtotal = $234,360

Grand Total All Awards = $937,440

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Mechanisms of Motor Neuron Injury in Acute Flaccid Myelitis

Award Number: K08NS124989

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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