Rycal® Science


Rycals®: the next big thing in small molecules

  An inspiring new direction in therapy for the leading causes of morbidity and mortality, Rycals are small-molecule therapeutics developed in the laboratory of Dr Andrew R. Marks at Columbia University in New York, NY. Specifically, Rycals are calcium release channel stabilizers that show great promise in the treatment of debilitating cardiac, skeletal muscle, and neurological disorders.

Signaling a new chapter in restorative function

  In chronic debilitating diseases (eg, heart failure, muscular dystrophy, neurodegenerative disorders), activation of stress pathways causes post-translational RyR modifications such as PKA-phosphorylation, oxidation and/or nitrosylation, which in turn causes Calstabin® to dissociate from the ryanodine receptor channel, resulting in leaky calcium channels. When calcium is continuously leaked—rather than released in natural, highly regulated processes—contraction of heart and skeletal muscle is weakened and neurologic function is impaired.
  ARMGO has used a proprietary Calstabin binding screen to identify compounds that normalize leaky RyR channels. These compounds, named Rycals, can enhance the binding of Calstabin to the leaky ryanodine receptor/calcium release channels that are present inside virtually all cell types. The enhanced binding of Calstabin to the RyR channels stabilizes the closed state of the channel in a natural manner; this repairs the leak in the RyR channel and restores its normal function in muscle and brain tissues. It is important to note that, to date, the Rycal compounds have no demonstrated measurable activity on normal, non-leaky RyR channels.
  Recently, defects in ryanodine receptor function have been associated with several disorders, including:
  • Heart failure
  • Cardiac arrhythmias
  • Skeletal muscle disorders
  • Cognitive function

Why such strong promise

  By stabilizing the ryanodine receptor/calcium release channel via enhancing the binding of Calstabin to the leaky RyR channels, it may be possible to restore the strength of muscle contraction, which could potentially result in improvements in heart function and skeletal muscle strength. In addition, calcium leak via RyR channels in the brain may impair cognitive function and cause seizures. Therefore, by stabilizing the RyR channel function, Rycal compounds may improve cognitive function and prevent seizures. For both physicians and patients, Rycal compounds represent a potential new and welcome alternative in the treatment of chronic, debilitating disorders.
  • Selected Publications

Rycal® Stabilizing Video