Combination Therapy for a Safer Treatment of Heart Failure

Lichtstein David, HUJI, School of Medicine - IMRIC, Medical Neurobiology
Gibson Dan, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research



Congestive heart failure (CHF) is a chronic progressive disease that affects the pumping power of heart muscles.  The disease is one of the leading causes of death and disability in the world. Almost 6 million Americans now suffer from heart failure, a figure that according to the WHO is expected to increase by 46 percent - to nearly 9 million - by 2030.  Treatment for the disorder includes changes in lifestyle such as an improved diet, as well as various medical treatments. For more than 200 years, CHF has also been treated with plant-derived cardiac steroids (CS), such as digoxin, which increase the force of contraction on a failing cardiac muscle. The use of digoxin, however, is limited by its narrow therapeutic window and its toxicity.

Our Innovation

We have discovered the molecular mechanisms underlying the effectiveness CS as a drug to treat CHF. Consequently, we have proven that combining CS treatment with AKT inhibitors dramatically increases the therapeutic window of CS, hence increasing its efficiency.


The beneficial effects of combining CS treatment with AKT inhibitors (both at extremely low doses) was proven in five experimental systems: 1. Zebrafish cardiomyocytes; 2. Zebrafish in-vivo; 3. Rat cardiomyocytes; 4. Isolated heart preparation (Langendorff); 5. Rat in-vivo following ischemia (LAD-ligation).  In all of these systems ,the addition of an AKT inhibitor caused the potentiation of CS (digoxin, ouabain and bufalin). Doses of CS that when given alone did not affect heart contractions at all, significantly increased the contraction force when given together with the AKT inhibitor.

This technology is IP-protected, and research results were published in the scientific literature.


There is a constant need for novel cardiotonic drugs. Our work has established a proof of concept that the combined treatment of CS with AKT inhibitors increases the efficiency of these steroids and opens a new venue for treatment.

As noted, CS are extremely potent drugs, but their long term use is problematic due to their toxicity. Nevertheless, the continuous use of CS, despite the toxic manifestations, attests to the importance of this class of drugs in treating CHF. Our technology has the advantage of reducing the needed dose of CS and increasing its therapeutic window.

Contact for more information:

Mel Larrosa
VP Business Development Healthcare