Our Science

Targeting ryanodine receptors to treat serious diseases

Ryanodine receptors (RyRs) are ion channels that regulate the intracellular flow of calcium in nearly all cell types. Because of their central role in human biology, RyRs are promising therapeutic targets that have been linked to a wide range of indications including serious cardiovascular disorders and skeletal myopathies.

Our novel class of small molecule investigational therapeutics called Rycals® are designed to repair RyRs which are essential for muscle function. Leaky receptors, which allow calcium ions to abnormally flow from the sarcoplasmic reticula into the cytoplasm, contribute to the progression of life-threatening cardiovascular and skeletal muscle diseases.

Ryanodine receptor channels effect muscle contraction through regulation of intracellular calcium ions

A ryanodine receptor (RyR) channel is closed during muscle relaxation

In normal functioning, calcium ions are stored in the sarcoplasmic reticulum (SR) when the ryanodine receptor channels are closed, which allows the muscle cell to relax.

External stimulus causes the RyR channel to open

The release of stored calcium ions into the cytoplasm via open ryanodine receptor channels triggers muscle contraction. To facilitate cycles of muscle contraction and relaxation, SERCA pumps calcium ions back into the SR.

Leaky RyR channels interfere with normal calcium cycling

In a diseased state, leaky RyRs cause dysregulated flow of calcium ions into the cytoplasm, disrupt muscle function and drive excessive ATP consumption from the additional burden on SERCA.

Mechanism of ARM210

Our lead drug candidate ARM210 is a Rycal® designed to repair RyRs that are leaky due to either genetic mutations or post translational modifications that accrue from physiological and cellular stress. Rycals® are allosteric modulators of ryanodine receptors that preferentially bind to leaky ryanodine receptors without blocking the calcium channel.

Normal (Closed State)

RyRs regulate the flow of calcium ions in and out of the sarcoplasmic reticulum (SR), an intracellular storage organelle.

Leaky

RyR conformation is altered due to genetic mutations or post translational modifications. Unregulated flow of calcium ions contributes to the progression of life-threatening cardiovascular and skeletal muscle diseases.

Repaired (Closed State)

Rycals are small molecule allosteric modulators that bind to RyRs, repair leaks regardless of their cause and restore normal function.

RyCarma is developing ARM210 to address RyR dysfunction contributing to the progression of cardiac and skeletal muscle indications regardless of the underlying cause of receptor malfunction.

Learn more about our pipeline
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