Wednesday, December 31, 2025 12/31/2025

Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signatures

Award Number: R01NS120926
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: 05/15/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signatures - ABSTRACT The immune system contributes to amyotrophic lateral sclerosis (ALS) progression and survival, and therapies to target the immune system are of burgeoning interest. However, the changes in the immune system during the course of ALS and the sex-specific alterations in immune function warrant a more in depth analysis in order to develop personalized ALS therapies and biomarkers. The long-term goals are to harness the immune sys- tem’s potential to slow and stop the progression of ALS. The overall objective is to determine how peripheral immune profiles, sex, age, and sex hormones, link to neuronal damage, neuroinflammation, and ALS progres- sion and survival. The central hypothesis is that peripheral immune profiles are an important pathophysiologic agent of ALS progression and survival; that sex, age and sex hormone levels impact these profiles; and that insight into ALS patient-specific immune profiles will yield new drug targets and therapeutic windows. Our ra- tionale is that linking patient-specific immune cell profiles to ALS progression and survival will facilitate person- alized immunomodulatory therapeutic development for ALS and identify potential treatment windows. The cen- tral hypothesis will be pursued with three aims: 1) Identify specific immune profiles that associate with ALS pro- gression and survival rates.; 2) Evaluate the effects of sex hormones on ALS immune profiles, progression, and survival; and 3) Identify immune profiles and corresponding cellular pathways that are most toxic to neu- rons and that associate with central inflammation. In Aim 1 longitudinal immunophenotyping of peripheral blood samples from ALS subjects will generate composite immune profiles that will then be linked to ALS subject characteristics, progression, and survival. Aim 2 will determine if observed sex-dependent associations be- tween immune profiles and ALS progression and survival are mediated by sex hormones, as sex hormones can alter immune profiles. Aim 3 will enrich a cohort of ALS subjects by immune profile clusters; their periph- eral immune populations will be analyzed using 1) RNA-seq and 2) cell toxicity studies via co-cultures with iPSC-derived neurons; subjects will also have positron emission tomography (PET) imaging to quantify central neuroinflammation. Datasets will be synthesized to build prediction models and create deep neural networks capable of associating immune profiles with sex, age, disease severity, progression, and survival The research proposed is innovative, in the applicants’ opinion, because it rigorously examines the effects of sex, age, and sex hormone levels on immune cells and ALS progression and survival in a longitudinal study. It also accounts for the interactions between immune cells by forming immune profiles for individual subjects and assesses how specific profiles associate with dysregulated pathways, cytotoxicity, and neuroinflammation. The proposed re- search is significant because it will provide critical data on the distinct immune profiles and pathways associ- ated with ALS progression and survival in a sex-, age- and sex hormone- specific fashion.


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	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $515,683 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/23/2025	NON-COMPETING CONTINUATION	$515,683
														Subtotal = $515,683

Issue Date FY: 2024 ( Subtotal = $568,145 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/3/2024	NON-COMPETING CONTINUATION	$41,000
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/15/2024	NON-COMPETING CONTINUATION	$527,145
														Subtotal = $568,145

Issue Date FY: 2023 ( Subtotal = $613,303 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/9/2023	NON-COMPETING CONTINUATION	$613,303
														Subtotal = $613,303

Issue Date FY: 2022 ( Subtotal = $633,717 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/1/2022	NON-COMPETING CONTINUATION	$63,373
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/11/2022	NON-COMPETING CONTINUATION	$570,344
														Subtotal = $633,717

Issue Date FY: 2021 ( Subtotal = $643,473 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/8/2021	NEW	$643,473
														Subtotal = $643,473

Grand Total All Awards = $2,974,321

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Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signatures

Award Number: R01NS120926

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: 05/15/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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