Tuesday, November 4, 2025 11/4/2025

Novel Approaches to Therapy of Muscle Ion Channelopathies

Award Number: R01AR074985
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Novel Approaches to Therapy of Muscle Ion Channelopathies - We will study mouse models of two muscle diseases with abnormal electrical activity. In myotonia congenita, hyperexcitability is caused by loss of function mutations in the muscle ClC- 1 chloride channel (an anti-excitability subthreshold current). Myotonia (muscle stiffness) is caused by unwanted firing of action potentials. Hyperkalemic periodic paralysis (HPP) is caused by gain of function mutations in the muscle Nav1.4 sodium channel, which increase a non- inactivating Na current (Na persistent or NaP). Patients with HPP suffer from both myotonia and attacks of weakness caused by depolarization of muscle by NaP, which inactivates the Na current responsible for action potentials (Na transient current, NaT). We will determine whether block of NaP rather than NaT is the mechanism underlying efficacy of Na channel blockers in treating myotonia congenita. We will use a genetic, a pharmacologic and a computer model of myotonia congenita to examine the roles of NaP and NaT in triggering hyperexcitability. We will also determine whether selective block of NaP provides effective therapy for hyperkalemic periodic paralysis (HPP). Na channel blockers have surprisingly been ineffective in treating HPP. We hypothesize treatment failed because the blockers used were not selective for NaP so block of NaT worsened weakness. If we are correct that NaP regulates excitability, it would suggest the approach to developing new Na channel blockers needs to be fundamentally altered. Instead of identifying drugs which block NaT, the goal would be to identify drugs which block NaP, but do not block NaT. Development of selective blockers of NaP could improve therapy of muscle channelopathies, cardiac arrhythmias, epilepsy and neuropathic pain.


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 = $570,251 )
2025	2025	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	4/14/2025	COMPETING CONTINUATION	$570,251
														Subtotal = $570,251

Issue Date FY: 2024 ( Subtotal = $521,839 )
2024	2024	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	6/4/2024	NON-COMPETING CONTINUATION	$37,658
2024	2024	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	1/11/2024	NON-COMPETING CONTINUATION	$484,181
														Subtotal = $521,839

Issue Date FY: 2023 ( Subtotal = $537,978 )
2023	2023	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	2/23/2023	NON-COMPETING CONTINUATION	$53,797
2023	2023	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	2/8/2023	NON-COMPETING CONTINUATION	$484,181
2023	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	11/30/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $537,978

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $584,689 )
2021	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/5/2021	SUPPLEMENT FOR EXPANSION	$62,849
2021	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/3/2021	NON-COMPETING CONTINUATION	$521,840
														Subtotal = $584,689

Issue Date FY: 2020 ( Subtotal = $600,827 )
2020	2020	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/1/2020	NON-COMPETING CONTINUATION	$600,827
														Subtotal = $600,827

Issue Date FY: 2019 ( Subtotal = $589,512 )
2019	2019	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/18/2019	NEW	$537,978
2019	2019	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	6/27/2019	SUPPLEMENT FOR EXPANSION	$51,534
														Subtotal = $589,512

Grand Total All Awards = $3,405,096

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Novel Approaches to Therapy of Muscle Ion Channelopathies

Award Number: R01AR074985

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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