A new therapeutic approach could help millions of patients to prevent the late effects of a heart attack - the excess formation of scar tissue. Philip Wenzel and Wolfram Ruf from the Mainz University Medical Centre and the German Centre for Cardiovascular Research (DZHK) have been granted a patent for this. The underlying reason is that heart attacks are often recognised too late - with fatal consequences: The blocked vessel cannot be opened in time and heart tissue dies. If the new therapy reaches the clinic, it could limit this damage in future.
During a heart attack, a blood vessel that supplies the heart with oxygen is obstructed. If the blockage is not cleared quickly enough - for example because the heart attack goes unnoticed or treatment is too late - the undersupplied heart tissue dies. After the infarction, the body attempts to break down and replace the damaged tissue, which is accompanied by inflammatory processes.
‘Inflammation after a heart attack is necessary for the removal of dead tissue. But if it is too strong, the heart can be further damaged,’ says Prof Dr Philip Wenzel from the Mainz University Medical Center. Excessive inflammation also attacks healthy tissue and leads to excessive scarring. This causes the heart to lose elasticity and pumping power.
Women are particularly at risk - because their symptoms are often unrecognised
Women are particularly often treated too late, as their symptoms do not correspond to the classic idea of a heart attack. While men often complain of the typical chest pain radiating to the left arm, women often have non-specific symptoms such as nausea, sweating, shortness of breath or back pain.
‘It is absurd that these complaints are considered ‘atypical’. Women are no exception - they make up half of the population. Because their symptoms are not sufficiently recognised, many heart attacks go undetected,’ says Wenzel. If a heart attack is recognised too late, there is often no time left for reperfusion therapy, i.e. reopening the vessel with a balloon catheter.
For this group of patients in particular, the new therapy could be a valuable alternative to reduce consequential damage.
The solution: targeted blockade of the harmful signalling pathway
Wenzel and his team have discovered that the so-called TF-PAR2 signalling pathway plays a key role in this harmful inflammatory reaction. Tissue factor (TF) and protease-activated receptor 2 (PAR2) contribute to the excessive activation of certain immune cells, which leads to increased fibrosis and thus to a further deterioration in heart function. Precise and targeted intervention here can reduce persistent coagulation and inflammation - two factors that play a decisive role particularly in heart attack patients without reperfusion.
Wenzel's discovery describes a new method of specifically blocking this harmful mechanism. This can be done using special drugs, including anticoagulants, which interfere with this process, and monoclonal antibodies, which prevent the signalling pathway and switch it off. European patent EP4247408 has now been granted for this.
The scientific proof: animal studies show success
Experiments with mice showed that animals treated with the new method developed less fibrosis in the heart, retained better heart function and had a higher survival rate. ‘If this mechanism is blocked, the remodelling is less drastic. The left ventricle does not dilate as much and the heart's pumping function improves significantly,’ says Wenzel.
Treated mice had 50 per cent less scarring after a severe heart attack and their cardiac performance improved significantly. The mice in the treated group all survived, whereas 40 per cent of the animals in the control group died.
A new biomarker for early detection
In addition to the therapeutic approach, the patent describes a new method for identifying patients with a particularly high risk of heart failure at an early stage. This involves analysing two biomarkers in the blood: a special protein in immune cells that indicates an excessive inflammatory reaction and the inflammatory factor TGF-β1, which is associated with the development of fibrosis. Wenzel says: ‘With these biomarkers, we can see at an early stage which patients have a higher risk of severe heart failure - and treat them specifically.’
Inventor wants further development by companies
Further steps are now required for the therapy to reach clinical application. ‘We now have the patent, but for it to actually reach the clinic, a company needs to get involved in further development; we are currently working on this in our Clusters4Future application curATime. Production, conducting clinical trials and ultimately authorisation - this is not feasible for an academic group alone.’ If this succeeds, the therapy could become an important addition to the treatment of heart attack patients in the future.
Link to the Patent database: https://register.epo.org/application?number=EP21820471
