Congestive Heart Failure
Congestive Heart Failure (CHF) is a condition which affects large numbers of individuals, and is characterized in large part by a reduction of exercise capacity. Weakening of the heart muscle prevents it from pumping the volume of blood necessary for normal oxygenation of tissues and organs. Because the RBC's normally release only 25% of their bound oxygen, the heart pumps a smaller volume of blood which does not sufficiently oxygenate the organism. The limited delivery of oxygen is the major cause of decreased exercise capacity in patients with CHF.
OXY111A, NormOxys' lead drug candidate, modifies hemoglobin's affinity for oxygen and enables an enhanced, regulated oxygen delivery. In mice with severe heart failure, administration of OXY111A led to a dose related increase in maximal exercise capacity of 63 ± 7%.
OXY111A decreases the oxygen binding affinity of hemoglobin, increases tissue oxygen delivery and substantially increases the maximal exercise capacity in normal mice and mice with severe heart failure. OXY111A is thus an attractive candidate for the therapy of patients with reduced exercise capacity caused by heart failure.
OXY111A Restores Exercise Capacity in Mice
OXY111A restores exercise capacity in mice with severe heart failure. Transgenic mice with cardiac-specific over-expression of Gαq have an approximately 40 % reduction in maximal exercise capacity compared to normal mice. Distance run at baseline (B) and 16 - 24 hours after administration of OXY111A (T) or placebo. n = 5 - 6 per group.
The baseline maximal exercise capacity in mice with severe heart failure is only ~60% of that in normal mice. As demonstrated above, OXY111A administration caused striking dose-related increases in maximal exercise capacity in these animals of 34% at 1 g/kg (brown bars) and 71% at 2 g/kg (blue bars).