Pulmonary arterial hypertension (PAH) is a very severe diagnosis. In its severity, this disease is comparable to lung cancer and is characterized by high pressure in the blood vessels that supply the most important organ of the respiratory system. The main risk factor is the formation of blood clots in the lungs and sleep apneawhich is characterized by the cessation of pulmonary ventilation during sleep.
Drug therapy in children with PAH has improved in recent years with the use of phosphodiesterase type 5 (PDE5) inhibitors, a vasodilator that blocks the damaging effects of PDE5. But despite the obvious advances in treatment, PAH remains an incurable disease. And in seriously ill babies, lung transplantation is inevitable sooner or later. Therefore, another way to treat the disease is needed.
A team of doctors led by Prof. Georg Hansmann from the Clinic for Pediatric Cardiology and Pediatric Intensive Care at the Hannover Medical School (MHH) tested a completely new method of individual treatment on a three-year-old patient for the first time in the world, namely, stem cell therapy derived from umbilical cord blood. . Impressive results have been published recently.
Worst prognosis of any known gene mutation
Pulmonary arterial hypertension, which the girl suffers from, is caused by a mutation in the ACVRL1 gene, which suppresses angiogenesis, the process of formation of new blood vessels in organs and tissues. “These mutations can occur spontaneously or be inherited, with the ACVRL1 mutation having the worst prognosis of all known gene mutations. So far, only seven PAH patients have been known to have this mutation worldwide,” Hansman said in an interview with Kardiologie. org.
It all started with the fact that the child had two seizures, which the doctors mistook for febrile convulsions – a common disorder among children caused by a jump in temperature and associated with oxygen starvation of the brain. The diagnosis turned out to be wrong. A more thorough examination revealed that the child’s ability to cope with stress was impaired.
The girl is fragile and small for her age. In addition, she had telangiectasia, a persistent vasodilation of the skin, manifested in the form of spider veins and accompanied by spontaneous nosebleeds. Such symptoms are characteristic of mutations in the ACVRL1 gene. On cardiac echocardiography, cardiologists found severely impaired right ventricular function with grade II tricuspid valve insufficiency. Catheterization showed extremely high pulmonary arterial pressure – 119/57 mm Hg. Art. at a rate of 25-30 mm Hg. Art.
“Lung transplant at this age is not the best option”
The little patient was referred to MHH for evaluation for a lung transplant. However, Professor Hansman immediately said that a lung transplant is not the best option for a three-year-old child. Therefore, at the first stage of treatment, MHH specialists tried to change the drug therapy, as a result of which the girl’s condition somewhat stabilized. The distance that she covered on foot became a little longer, but her body weight and height remained practically unchanged.
At this stage, it was decided to test therapy using human mesenchymal stem cells (MSCs) from the umbilical cord. And since the girl’s mother was at that time pregnant with her second child and was about to give birth, the doctors decided to use the umbilical cord of the newborn. Although, in principle, as Professor Hansman emphasizes, mesenchymal stem cell donors do not have to be family members: MSCs are distinguished by immune tolerance.
Strictly speaking, the Hanoverian doctors did not treat pulmonary hypertension with stem cells per se, but with a conditioned medium, that is, a “supernatant” of stem cell cultures. This is a common procedure with other stem cell treatments as well. By the way, the possibility is not excluded that the therapeutic effect is caused not by the cells themselves, but by the cytokines they produce – secreted proteins that stimulate and multiply immune cells.
Therapeutic effect of stem cell treatment
Treatment of a three-year-old patient lasted six months. During this time, five products from mesenchymal stem cells derived from the umbilical cord were gradually introduced into her body, or rather into the bloodstream. Two infusions were made into the pulmonary arteries, three through the central venous line.
The girl underwent the course of treatment without problems, and the therapeutic effect in the end was simply impressive: the child not only experienced a clear improvement in well-being, but also had no undesirable side effects. Already three months after the start of infusions, the patient grew by 10 centimeters. She also had a significant increase in body weight.
The treatment resulted in an improvement in exercise tolerance and clinical parameters of the cardiovascular system. In 6 minutes of walking, the girl began to overcome not 370, as before, but 485 meters. The pressure in the pulmonary artery decreased by a quarter, and the function of the right ventricle of the heart was basically normal.
Three years have passed since then. And so far the child feels fine. The disease that the girl suffers, of course, is not completely cured, but the treatment carried out according to the new method made her life quite full.
It was the first successful therapy for a person suffering from severe forms of PAH. But why has the effect of stem cell treatment been so persistent? Studies conducted by MHH experts have shown that umbilical cord stem cell “cocktails” can not only improve regeneration in damaged blood vessels, but also suppress their inflammation and prevent damage to certain parts of the cells. In any case, clinical studies will continue. And their target now may be a target group of patients, which includes young people with early stage pulmonary arterial hypertension. It is of particular interest to scientists.