# Novel Approaches to Therapy of Muscle Ion Channelopathies

> **NIH NIH R01** · WRIGHT STATE UNIVERSITY · 2020 · $600,827

## Abstract

NIH abstract:
Myotonia congenita (MC) and hyperkalemic periodic paralysis (HPP) are inherited skeletal muscle ion
channel diseases. Despite initial descriptions of both diseases many years ago, effective and well
tolerated therapy for both disorders has remained elusive. The reason for this is that a detailed
understanding of mechanisms regulating muscle excitability in health and disease is lacking. A better
understanding of mechanisms underlying muscle dysfunction in the non-dystrophic ion channelopathies
is necessary to develop improved therapy for patients.
While it is known that muscle in myotonia congenita is hyperexcitable due to reduction of ClC-1 current,
the mechanisms underlying two motor symptoms suffered by patients remain poorly understood. The
first is transient weakness in recessive forms of myotonia congenita (Becker disease). While the
weakness lessens with continued exercise, it is likely a significant contributor to motor dysfunction.
Weakness appears to be due to loss of muscle excitability, but the mechanism is unknown. The second
symptom is stretch-induced (percussion) myotonia. As muscles must alternately contract and stretch
during movement, stretch-induced myotonia may contribute significantly to stiffness. Currently, nothing
is known about the mechanism triggering stretch-induced myotonia.
We have discovered novel currents that underlie both weakness and stretch-induced myotonia. In Aims
1 and 2 our goal is characterize these currents and to test the efficacy of available blockers to develop
novel therapy for motor dysfunction in myotonia congenita. In Aim 3 we extend this work to study of
motor dysfunction in hyperkalemic periodic paralysis.

## Key facts

- **NIH application ID:** 9895630
- **Project number:** 5R01AR074985-02
- **Recipient organization:** WRIGHT STATE UNIVERSITY
- **Principal Investigator:** MARK M RICH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $600,827
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895630

## Citation

> US National Institutes of Health, RePORTER application 9895630, Novel Approaches to Therapy of Muscle Ion Channelopathies (5R01AR074985-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9895630. Licensed CC0.

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