Chronic Heart Failure (CHF) is a clinical syndrome associated with high morbidity and mortality globally, which seriously affects people’s quality of life. More than 12 million people suffer from CHF in China and the United States alone. Patients with the most advanced symptoms (classified as New York Heart Association (NYHA) class IV), which account for 10% to 15% of all CHF patients, are mostly bedridden and experience symptoms even while at rest. The annual mortality rate for these patients is over 50%, which is considerably higher than that for many types of cancer. Currently, standard treatment for CHF mainly reduces the workload of the heart by lowering blood pressure or slowing the beating rate of the heart.  However, such treatments provide limited benefits to NYHA Class IV patients, so novel therapeutic agents or treatment methods for are urgently needed for these patients.

A new enzyme called cardiac-specific myosin light chain kinase, or cMLCK for short, was discovered by Zensun scientists during investigations on the mechanism of action of Neuregulin. The cMLCK protein is found inside the cell, downstream of the receptors for Neuregulin that sit on the outside of the cell.  When Neuregulin binds to the receptors on heart cells, it causes the amount of cMLCK inside the cell to increase.  This elevates the activity of cMLCK, which boosts the construction of muscle fibers inside heart cells and ultimately improves the ability of the heart to pump blood.  For the most severe CHF patients, however, this signaling cascade cannot be initiated by treating heart cells with Neuregulin, because research has shown that the amount of the Neuregulin receptors on heart cells is reduced by more than 40% in these patients.  

What Zensun will be attempting to do for these patients is to bypass the Neuregulin part of the system by directly boosting the amount of cMLCK inside heart cells.  This can be achieved through what is called Gene Therapy, whereby copies of the gene for the cMLCK protein are added inside the heart cells.  Recent research has shown that a virus called an adeno-associated virus, or AAV for short, can be used to deliver copies of genes into cells without causing any disease itself.  Zensun has therefore begun using AAV to deliver the cMLCK gene into heart cells in order to increase the amount of the cMLCK protein. In early animal studies, Zensun has been able to achieve the same kind of therapeutic effects that have previously been seen with Neuregulin treatment, but in this case without the need to initiate the signaling through the Neuregulin receptor.

If the efficacy and safety of cMLCK gene therapy are confirmed when Zensun conducts clinical trials in CHF patients, this treatment will finally provide a targeted therapy that is specific for the most severe form of CHF.  The approval of such a therapy would not only fill the gap in treatment options that currently exists for NYHA Class IV patients, but would also improve the quality of life and extend the lifespan of these extremely ill patients that currently have very limited treatment options.