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Montreal medical treatment "Hail Mary" can save the lives of babies of the most common of all rare diseases


Montreal – Liang Deslauriers was born with eyes, magnetic, ethereal blue, low-set ears and a heart two sizes too big.

. It is thick, dense heart will continue to grow and threatens to kill Joliette, Que, small in front of her doctors Montreal tried something never before attempt – it is "Rejoice, Mary", which can transform the world's most widespread, incurable rare disease to a treatable one.

For the first time in the history of Noonan syndrome, a hereditary disease that prevents the different parts of the body to develop normally and that upsets one child in every 2500 births, Montreal doctors have changed the most mortal symptom of hypertrophic cardiomyopathy, an excessive thickening of the heart, which, in the most severe form, kills 70 percent children before they turn a year ago.

Doctors have used cancer drugs adapted to keep the heart of Liang essentially suffocate himself, and they are now preparing to discontinue treatment in the hope that the disease is essentially burned out. There is no guarantee, however, that he will not come roaring back.

We have a glimmer of hope here

"He can come back very quickly and is very difficult to control, or it can remain as it is," said pediatric cardiologist Dr. Gregor Andelfinger, from the Université de Montréal and Saint-Justine Hospital. "There is not a single study, no animal or human studies that can answer this question."

Lyana mother Lynne was in her eighth month of pregnancy, when a routine ultrasound revealed that some doctors in the former can not fully explain the structure of the heart Lyana looked away.

More sophisticated scan showed all four valve flaps that open and close each beat of the heart that allow blood to flow in or out, were normal, and the heart muscle thickness restless.

Lynn was in the hospital before Liang was born in November 2017, and if the child she was taken to whip in the neonatal intensive care unit before Lynn could hold or see her. He was there the picture became clear: a person Liang in – extra fold of skin at the inner corner of the eye, grove between the nose and mouth – says Noonan, and even the time to get involved in the blood and proper genetic testing done when Andelfinger saw Liang for 24 hours after her birth, he wrote in his notes, «RASopathy likely."

Noonan syndrome of & # 39 is RASopathy. RAS genes make proteins that control how cells communicate with each other. Chain proteins transmit signals from the loading dock outside the cell to the nucleus inside both runners in the relay, which pass the baton. When was the last runner in the cell-signaling pathway reaching the nucleus, the cell is instructed to respond in one of several ways: divide, multiply or die.

Liang Deslauriers held dad Joel as they meet with Dr. Gregor Andelfinger at Children's Hospital Sainte Justine in Montreal.

Christinne Muschi / National Post

Since mutations in RAS genes Nun become hyperactive, disrupting the normal flow of a call between cells. Cells can start proliferating Var & # 39; Jacek, causing hyper or too little growth in the affected tissues. Children may develop additional folds or neck lift. They may have a recessed or protruding chest. About a third are born with some sort of heart disease – it is not as potentially deadly as a rapidly progressive hypertrophic cardiomyopathy, the condition is life threatening in the Liang.

Muscle cells grow too thick as it makes the heart as a whole. Muscle strains, which makes it difficult for the body to relax, and thickeners blocks the flow of blood from the heart – and then usually only affects the left ventricle, the main pumping chamber, the two sides Liang's heart was closed. So were her valves.

Children with severe hypertrophic cardiomyopathy have a "terrible natural history," said Andelfinger. In the end, their hearts just to be. Only 30 percent were still alive at 20 per cent during the year. Two years survival rate or less. The best hope with a & # 39 is heart transplant, which means waiting, desperate and often in vain, for another child to die It also means trading one problem for another:. a new heart for lifelong anti-rejection drugs that increase the risk of developing cancer.

It was difficult at first for Lynn and her husband Joel digest what the doctors told them. Liang was a big baby, weighing more than four and a half kilograms at birth. She fed well. Everything seemed normal, except that her hands and feet were blue – a sign of how hard her heart straining to circulate blood.

Three days after the birth, doctors began Liang to standard treatment – aggressive doses of propranolol, a drug that reduces the force of contraction of the heart muscle. But with every week her heart became thicker.

When they grew up in propranolol, a team of Montreal is considered a mechanical device to help, man-made pump that can temporarily help the heart. But with very young children, with a small, beaded heart, it is extremely difficult to get the device. Alternatively, the shaving operation was part of the heart muscle, a procedure that is supplied with a high frequency of complications. "This is one of the operations that you do not really want for your children," said Andelfinger.

They need something to buy time and quickly.

Andelfinger reached out to Dr. Bruce Gelb, a pediatric cardiologist at Mount Sinai Hospital in New York, who discovered some of the earliest genes Nun. Zhelb knew another child in Germany with another mutation in the same gene as the Liang, who was even more severe, connected to the unit mechanical ventilation in the ICU.

Montreal and German researchers entered the literature. For many years, scientists have begun to understand that the mutations that control the overlap of Nun with mutations that control about a third of human cancers – solid tumors, such as breast cancer, lung cancer and melanoma. Teams began to experiment with mice genetically engineered to develop human Nun. When mice were treated with anti-cancer drug that blocked the growth cycle, effects disappeared.

The researchers began administering the drug trametinib Liang cancer and its German counterpart. "We explained to the parents," said Andelfinger. Lynn and her husband, Joel said that there were no guarantees of success, and no guarantee that there will be no "adverse effects." The parents agreed. "These children were very sick, both of them," said Zhelb. "Trying to Hail Mary is allowed in such circumstances, to be honest."

Treatment started when Liang was 14 weeks. Doctors could not "go gangbusters" at the highest doses, Zhelb said. This would risk excluding the child's bone marrow. They also do not want to kill the cells of the heart, just to stop them from multiplying so fast. Deregulation and the heart is too thin. "It's not like a flamethrower," said clinical pharmacist Christopher Marquis, Sainte-Justine, a member of the research team. "It acts like a sniper on a specific mutation and the enzyme."

Dr. Gregor Andelfinger meets with his patient and two-year-old Lyana Deslauriers (below) and her family & # 39; and.

Christinne Muschi / National Post

But after three months of treatment, the improvement was dramatic: the heart of both babies started to decline. Now, after more than 17 months of treatment, Lyana heart has gone out of the heart to triple its normal size "to a large extent a normal heart," said Andelfinger. Excess tissue in the heart of the values ​​and reduced. The findings are published this week in the Journal of the American College of Cardiology. If they are kept in large studies, they will be unprecedented, "and so meaningful to seven & # 39; families whose lives this devastating problem of contact," said Zhelb.

For Lynn and by Joel, expecting her seventh child in August (Liang was their fifth), the last two and a half years was a corkscrew anxiety, blood tests, and not knowing what the future holds.

These are just two cases reported so far. "But I think it's very encouraging that the result for the two children, apparently, is very different from what usually happens to these children," said Zhelb. "We have a glimmer of hope here."

At the same time, Liang & # 39 is healthy and strong, longer than most her age. She loves animals and playing outside in the sand. She also loves children, small children. "This deal with sick children," Lin said. "They are well aware of the other.

"They have a special kind of strength."

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