Breakthrough could mean future cure for rare heart and lung disease

14 June 2015        

Picture of BHF Professor Nick Morrell from University of Cambridge

A protein that targets the effects of a faulty gene could offer the first treatment targeting the major genetic cause of Pulmonary Arterial Hypertension (PAH), according to research we funded.

The breakthrough is the latest development made possible by your support. Studies we helped to fund, dating back to 2000, showed the gene that causes PAH. That work showed the absence or reduced activity of a particular protein, bone morophogenetic protein type II receptor (BMPR-II), leads to PAH. BMPR-II is important to the normal function of the blood vessels of the lungs.

This new study led by BHF Professor of Cardiopulmonary Medicine Nick Morrell and published today in Nature Medicine, is the first to use a protein, called BMP9, to reverse the effects of reduced activity of BMPR-II and to reverse the disease itself. The study was conducted in mice and rats, but also using cells from people with PAH.

What is pulmonary arterial hypertension?

PAH is thought to affect around 6,500 people in the UK. It is a chronic and debilitating disease that affects the blood vessels in the lungs, leading to heart failure, and leaves sufferers feeling breathless and exhausted. Current treatments only target the symptoms and prognosis remains poor. The only effective cure is a lung, or heart and lung, transplant, which has associated risks and complications.

Kath had a heart and lung transplant because of PAH. You can read her story in Heart Matters here.

Once diagnosed with PAH, a person has a 30 per cent chance of dying within three years and the condition affects more women than men. Researchers speculate that this gender disparity is caused by pregnancy triggering the disease in genetically susceptible women or that oestrogen can affect the function of BMPR-II.

Making the discovery

The University of Cambridge team, with contributions from researchers at the University of Lincoln, Switzerland and the US, searched for a BMP protein that could enhance the function of BMPR-II to target the condition. The researchers firstly trialled different BMP proteins on lung blood vessel cells grown in a dish. This process showed BMP9 to be most selective, and therefore less likely to have negative effects on other cells.

This study used the first animal model, a mouse, which closely mimics the human genetic form of the disease. Ultimately though, the team showed that BMP9 treatment reversed PAH in three separate mouse and rat models. They found that the treatment works in mice with both the genetic form of the disease, and in acquired forms of PAH, where the cause is unknown.

Next steps

BHF Professor Nick Morrell, who led the research and is Director of our Centre of Research Excellence at Cambridge, said:

"The next step for our research is studies in people with pulmonary arterial hypertension – first, safety testing to ensure the compound can be given to people. But we're confident of passing this phase because BMP9 exists naturally in the body. We're just giving patients more of it."

Professor Jeremy Pearson, our Associate Medical Director, said:

"We're very excited by these results. This condition is horrible and an effective treatment that prevents the need for a transplant would be a game-changer.

"Clinical trials of the treatment in patients are still needed but these findings, from years of research supported by the BHF, offer real promise of a cure."

Future breakthroughs

This breakthrough was made possible by your donations. Help us keep funding more research that could lead to cures.