|Category||LifeSciences and BioTechnology|
|Keywords||congestive heart failure, atrial fibrillation, cardiac steroids|
|Current development stage||For Pharmaceutical development: TRL4 – PoC&Safety of candidate device or system is demonstrated in a defined lab or animal model|
Cardiac steroids are commonly used for the treatment of congestive heart failure and atrial fibrillation. They inhibit Na+/K+ ATPase activity, thus resulting in increased intracellular sodium and decreased intracellular potassium. In turn, the increased levels of sodium block the antiporter activity of the Na+/Ca2+ exchanger, resulting in accumulation of Ca2+ within the endoplasmic reticulum and mitochondria. Eventually, this allows for an increased release of Ca2+ from the endoplasmin reticulum in response to contraction stimuli, which increases the output force of the heart and increases its rate of contractions. However, the excessive intracellular calcium can result in delayed after-depolarizations, leading to dysrhythmias.
The known cardiac steroids (such as digoxin, ouabain or bufalin) have the severe disadvantage of being toxic at therapeutic doses, resulting in numerous side effects.
Novel Bufalin Derivatives interact with the Na+, K+-ATPase at a potency 10-100x higher than the cardiac steroids in use today, thus diminishing the drug toxicity.
A new class of novel steroids for treating heart failure, which are less toxic and more effective compared to their existing analogs. Cardiac steroids such as digoxin, ouabain and bufalin are highly toxic at therapeutic doses. Their novel analogs, interact with Na+, K–ATPase with high affinities and as such may be used as potent cardiotonic steroids.