Fighting heart disease with a new weapon
By Julian Paton FRSNZ
There are over 200,000 patients with heart disease in Aotearoa New Zealand. Many patients die within five years of a heart failure diagnosis. Finding a new way to treat this condition would meet a major unmet clinical need. A novel drug is showing promise for alleviating heart failure, a common condition associated with sleep apnoea and a reduced lifespan. The drug is known as AF-130, which blocks a type of purinergic receptor (specifically P2X3). This was tested in an animal model with severe heart failure and found to improve the heart’s ability to pump, but, equally important, prevented the associated disturbed breathing, which itself worsens heart failure. Thus, this drug may offer a two-for-the-price-of-one deal in that it is slowing the progression of heart failure and preventing dysfunctional breathing.
When a person has heart failure, the brain responds by activating the sympathetic system, the ‘fight or flight’ response, as a way to stimulate the heart to pump more blood to preserve life. Although this is a protective response initially, long term and persistent stimulation of sympathetic activity exacerbates the deterioration of the hearts’ condition and hence reduces life expectancy. The new drug is the first to temper the sympathetic nervous activity to the heart and, by doing so, reverses the heart’s progressive decline in heart failure.
The site of action for the drug includes a small organ – the carotid body, which also controls breathing. This allows the drug to perform its dual function of both reducing the ‘fight or flight’ response while also stimulating breathing to stop the apnoeas.
Although there have been several classes of drugs that have improved the prognosis of heart failure, none work in a way that this new agent does. It is promising to see a novel method that potentially reverses some features of heart failure and associated co-morbidities. The next step will be to see whether the beneficial effects seen with this drug in animal models will translate to humans.
Lataro, R.M., Moraes, D.J.A., Gava, F.N. et al. P2X3 receptor antagonism attenuates the progression of heart failure. Nat Commun 14, 1725 (2023).