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Intermittent Hypoxia Initiated Motor Plasticity in Individuals with Multiple Sclerosis

Award Number: R21HD108587
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/04/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Intermittent Hypoxia Initiated Motor Plasticity in Individuals with Multiple Sclerosis - PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system that causes localized damage to myelin, resulting in loss of function, disability, and reduced quality of life. Although disease-modifying drugs can help reduce the frequency of relapses and onset of new symptoms, this approach is insufficient for optimal recovery from existing symptoms. One potential approach to overcome functional impairments related to existing motor deficits is through development of therapeutic strategies that induce neuroplasticity. The objective of this proposal is to investigate the potential of a novel therapeutic intervention — Acute Intermittent Hypoxia (AIH) — that has shown significant promise to enhance neuroplasticity in persons with spinal cord injury but has not yet been studied in MS. AIH constitutes a brief, repeated reduction in oxygen concentration which stimulates the serotonergic pathway and enhances activity of serotonin receptors. This results in increased synthesis of plasticity-related proteins that potentiate synaptic transmission and drive plasticity. We hypothesize that a repeated AIH protocol will improve voluntary limb function in individuals with MS. We also hypothesize that AIH will induce sustained changes in neural activity within the central nervous system, which contribute to therapeutic plasticity. We test this hypothesis using a double-blind, sham-controlled and crossover trial in MS patients with established motor deficits and controlled relapse activity who are administered mild doses of intermittent hypoxia (or sham hypoxia) for five days. We examine the resulting effects by quantifying changes in strength, function and walking performance immediately and 1-week post-intervention. We also use advanced functional magnetic resonance imaging techniques to measure changes in neural activation during voluntary ankle flexion and intrinsic connectivity in the somatomotor cortices at rest, which have both shown plasticity-related changes during successful motor rehabilitation strategies. Additional clinical MRI scans at enrollment and 1-week post-intervention will be monitored for radiologic signs of new disease activity as part of participant safety monitoring. This proposal will determine the extent to which priming the central nervous system with an approach known to induce plasticity improves function in MS, and provide evidence of the neural mechanisms driving these therapeutic effects. The insights gained from this work will inform the development of more effective therapies combining daily AIH with task specific training for improvement of function and quality of life in individuals with MS.


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 = $0 )
2025	2024	REHABILITATION INSTITUTE OF CHICAGO	355 E ERIE ST	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	2	9/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $243,162 )
2024	2024	REHABILITATION INSTITUTE OF CHICAGO	355 E ERIE ST	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	001	2	8/7/2024	NON-COMPETING CONTINUATION	$243,162
2024	2023	REHABILITATION INSTITUTE OF CHICAGO	355 E ERIE ST	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	1	1/17/2024	NEW	$0
														Subtotal = $243,162

Issue Date FY: 2023 ( Subtotal = $218,185 )
2023	2023	REHABILITATION INSTITUTE OF CHICAGO	355 E ERIE ST	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	1	9/4/2023	NEW	$218,185
														Subtotal = $218,185

Grand Total All Awards = $461,347

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Intermittent Hypoxia Initiated Motor Plasticity in Individuals with Multiple Sclerosis

Award Number: R21HD108587

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/04/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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