Heart disease cured with a hormone-based drug already prescribed for breast feeding mothers.
German researchers have discovered that a drug commonly prescribed to new mothers to halt lactation also cures a rare type of heart failure known as postpartum cardiomyopathy (PPCM). The team made the discovery after accidentally designing an animal model that showed them exactly what caused the condition.
Denise Hilfiker-Kleiner from Hannover University and her team designed a genetic knockout mouse to study the function of an important transcription factor called Stat-3 (Signal transducers and activator of transcription 3), a protein that regulates cell proliferation. The modified mouse was missing the gene coding for Stat-3.
’We bred these mice and noticed that many of them did not survive multiple pregnancies. When we monitored them more closely, we discovered that this knockout was susceptible to this exact type of heart failure [PPCM] so we knew Stat-3 must be involved,’ co-author Helmut Drexler told Chemistry World.
The group showed that PPCM is caused when prolactin, a hormone released at birth to stimulate lactation, is converted into a smaller, biologically active peptide known as 16kDa prolactin. This smaller, nastier version of the hormone destroys the endothelial lining of blood vessels and reduces blood flow to the heart. Stat-3 prevents prolactin from being cropped down into this destructive peptide.
The researchers confirmed this by treating the pregnant knockout mice with bromocriptine, a drug that inhibits the release of prolactin. ’In our mouse model bromocriptine completely prevented PPCM,’ said Hilfiker-Kleiner.
Stat-3 increases the formation of antioxidant proteins, protecting the heart from oxidative stress. Without these antioxidants, stress on the heart cells leads to increased levels of the enzyme responsible for cleaving prolactin into its damaging counterpart.
PPCM is a very rare condition affecting one in every 1300 to 4000 deliveries in the US but, as Drexler emphasises, it leads to death in around a quarter of the women it affects and many of those who survive require a heart transplant. ’Since this affects a mother shortly after childbirth, it is especially traumatic,’ he said.
Fortunately, Bromocriptine is an established drug that has been used for years to halt lactation in new mothers. So it can be used directly to treat women with PPCM or with high risk for PPCM, Hilfker-Kleiner told Chemistry World.
Bromocriptine has already been trialled in a small preliminary study in 12 women with a high risk of PPCM and was shown to prevent PPCM. ’This was a preliminary trial. We need to prove the effectiveness of our therapy in a larger randomised and blinded trial, before we can be sure that it really works.’
et alCell, DOI:10.1016.j.cell.2006.12.036