Related Experiment Video

Updated: Aug 8, 2025

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

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Drug development for the treatment of RyR1-related skeletal muscle diseases

Takashi Murayama1, Nagomi Kurebayashi1, Ryosuke Ishida2

  • 1Department of Pharmacology, Juntendo University School of Medicine, Tokyo, Japan.

Current Opinion in Pharmacology
|February 26, 2023
PubMed

Insights

High-throughput screening assays offer new ways to find drugs for RyR1-related muscle diseases. These methods identify novel RyR1 inhibitors and modulators, paving the way for potential treatments.

Area of Science:

  • Muscle physiology
  • Pharmacology
  • Biochemistry

Background:

  • Type 1 ryanodine receptor (RyR1) is crucial for skeletal muscle excitation-contraction coupling.
  • RyR1 mutations cause severe muscle disorders like malignant hyperthermia and myopathies.
  • Current treatments for RyR1-related diseases are limited.

Purpose of the Study:

  • To review recent advancements in high-throughput screening (HTS) assays for RyR1.
  • To discuss the potential of HTS in discovering therapeutic candidates for RyR1-related muscle diseases.

Main Methods:

  • Development of FRET-based and endoplasmic reticulum Ca2+-based HTS assays.
  • Utilizing a reconstituted platform for HTS of excitation-contraction coupling modulators.

Main Results:

  • Identified novel RyR1 inhibitors using established HTS assays.
  • Enabled HTS for modulators of excitation-contraction coupling via a reconstituted platform.

Conclusions:

  • HTS assays represent a promising approach for identifying therapeutic compounds targeting RyR1.
  • Further development and application of HTS methods are crucial for advancing treatments for RyR1-related muscle diseases.

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