About Celladon's small molecule program
The initial focus of Celladon's SERCA small molecule program is the treatment of diabetes. It is now becoming recognized that obesity disrupts intracellular Ca2+ homeostasis and induces endoplasmic reticulum (ER) stress, leading to the accumulation of unfolded proteins in the ER. A high level of ER Ca2+ is imperative for maintenance of normal ER function and this high Ca2+ concentration of ER is maintained by sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Signs of ER stress have been found in liver and adipose tissue of obese mice and mice fed high-fat diets. Accumulating evidence suggests that ER stress plays a role in the pathogenesis of diabetes, contributing to pancreatic b-cell failure and insulin resistance. ER stress may also act as a link between obesity and insulin resistance in liver and adipose tissue, raising the intriguing possibility that the cellular ER stress response is a common mechanism for both b-cell dysfunction and defective insulin signaling in type 2 diabetes.
Celladon's novel approach is to develop pharmacological agents which correct this Ca2+ imbalance in the ER, via small molecule, allosteric SERCA2b agonists. These agents increase the Vmax of SERCA2b, increase Ca2+ content of the ER, effectively reduce the ER stress response, enhance glucose tolerance, and reduce hepatosteatosis.
Celladon is a privately held biotechnology company founded with the goal of becoming the leader in developing molecular therapies for the treatment of heart failure and cardiac diseases. The company's lead product, MYDICAR, targets the key enzyme deficiency in advanced heart failure, SERCA2a, which regulates calcium cycling and contractility in heart muscle cells. A recent Phase 2 clinical trial demonstrated sustained improvement at one year in cardiac function parameters and quality of
|SOURCE Celladon Corporation|
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