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Intermuscular coherence: A novel biomarker for upper motor neuron dysfunction in ALS

Award Number: R01NS116262
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: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Intermuscular coherence: A novel biomarker for upper motor neuron dysfunction in ALS - Project Summary/Abstract Amyotrophic lateral sclerosis (ALS) is a uniformly fatal neurodegenerative disease caused by neuronal death in the motor system, both in the brain and spinal cord. It results in progressive weakness throughout the body, with death typically from respiratory failure within 3 years of symptom onset. Therapy initiation and drug development are hindered, in part, by the lack of quantitative biomarkers for the disease. In the proposed project a multi-center study will be carried out to validate and further characterize a potential biomarker for ALS, known as intermuscular coherence (IMC). IMC measures the correlation of activity between two muscles and represents the shared input to the muscles from motor neurons in the brain and spinal cord. In vivo studies in both non-human primates and humans suggest that IMC in the range of 15-40 Hz (β-to-γ frequencies) represents input to muscle pairs from upper motor neurons. When motor neurons in the brain are damaged, as happens in ALS, IMC decreases in the βγ frequency range. In a preliminary report we showed that patients with ALS have lower IMC in the βγ range than do age- and sex-matched control subjects. Because the measurement of IMC is quick, non-invasive, painless, and requires only equipment found in standard clinical neurophysiology labs, the method, if validated, would be an important biomarker for ALS. Proposed is a multi-center validation study of IMC in the clinical environment. First, the accuracy, sensitivity, and specificity of the biomarker will be determined in patients who present to neurology clinic for an initial evaluation when ALS is suspected. In order to provide the most specificity, the distribution of IMC values will be characterized in neurotypical subjects across several demographic subgroups. Finally, IMC will be monitored over time in patients with ALS to determine how IMC changes with ALS disease progression. Preliminary data suggest that IMC could be a useful biomarker for diagnosing ALS, allowing differentiation of ALS from ALS-mimic disorders, and that it can be used to objectively monitor the progression of ALS over time. A multi-center study to test the validity of these preliminary findings is important before this method can be implemented to speed diagnosis and provide faster access to treatments of ALS for patients.


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 = $538,546 )
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/22/2024	NON-COMPETING CONTINUATION	$538,546
														Subtotal = $538,546

Issue Date FY: 2024 ( Subtotal = $505,731 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	12/4/2023	NON-COMPETING CONTINUATION	$538,546
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	4/25/2024	NON-COMPETING CONTINUATION	$41,888
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/21/2023	SUPPLEMENT FOR EXPANSION	-$74,703
														Subtotal = $505,731

Issue Date FY: 2023 ( Subtotal = $673,087 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/30/2023	NON-COMPETING CONTINUATION	$59,838
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/2/2022	NON-COMPETING CONTINUATION	$538,546
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	4/7/2023	SUPPLEMENT FOR EXPANSION	$74,703
														Subtotal = $673,087

Issue Date FY: 2022 ( Subtotal = $598,384 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/24/2022	NON-COMPETING CONTINUATION	$59,839
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/26/2021	NON-COMPETING CONTINUATION	$538,545
														Subtotal = $598,384

Issue Date FY: 2021 ( Subtotal = $645,031 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/26/2020	NEW	$640,261
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	1/18/2021	NEW	$4,770
														Subtotal = $645,031

Grand Total All Awards = $2,960,779

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Intermuscular coherence: A novel biomarker for upper motor neuron dysfunction in ALS

Award Number: R01NS116262

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: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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