You will walk, and not under yourself

Innovation between life and death

Galina Kostina, "Expert" No. 26-2014

Discoveries made by scientists who have dug up to the molecular level in cells, and new technologies in the field of medical equipment over the past 15-20 years have allowed doctors not only to cure patients and significantly prolong their lives, but also to make this life better.

A young woman, hearing the terrible diagnosis of breast cancer, burst into tears. "Wait a minute," the doctor reassured her. "You didn't hear the rest of it, it's being treated." She didn't even understand right away, she had to repeat it twice, explaining that she was lucky not only that the disease was caught at an early stage, but also that there are effective drugs. Who would have believed this even twenty years ago, when cancer was almost unconditionally considered a death sentence? Biology, followed by medicine, is moving with fantastic acceleration. The whole XX century is full of scientific discoveries that not only shocked scientific minds, but also provided doctors with medicines and tools. It is enough to recall the creation of vaccines and antibiotics, the discovery of the structure of DNA, the beginning of the era of genetic engineering, which gave human proteins — insulin, interferon and others, the creation of the method of in vitro fertilization, organ transplantation, ultrasound, computed tomography, MRI. Only at the beginning of the XXI century, several epoch—making discoveries were made, among them the completion of the Human Genome project, the creation of induced pluripotent cells from an adult skin cell, as well as technologies for creating a brain-prosthesis interface via a computer. All this is seriously changing medicine

The first places in mortality in the world are occupied by cardiovascular and oncological diseases. In terms of coverage, diseases of the nervous system are quickly selected to the leaders. Therefore, most of the innovations are in these areas. In particular, in the portfolios of pharmaceutical companies in 2012 there were more than 2,500 antitumor and related developments

Half of them are already cured, many people are really in the dark about new advances in oncology. Cancer is still terrifying. Meanwhile, over the past two decades, perhaps the most innovations have been created in this area. And some of the numbers are simply amazing. "Now breast cancer diagnosed at the initial stage is treated in 90-92 percent of cases," says the chief physician of the 62nd Cancer Hospital, Honored Doctor of the Russian Federation, Professor Anatoly Makhson. "According to our data, the five—year survival rate, in particular in Moscow, of patients with all types of cancer has reached 50 percent." It is believed that in the vast majority of cases, progression or metastasis may occur within five years after treatment; if this does not happen, the patient is considered cured

"Over the last decade, a completely different understanding of oncological diseases has come," says Vitaly Prutsky, head of information support at AstraZeneca R&D company. — The level that was previously taught in medical institutes now seems superficial. When scientists delved into the subject and descended to the molecular level, the processes of tumor development due to breakdown or, conversely, strengthening of some biological mechanism became clear. This knowledge makes it possible, as a result of an active search, and sometimes even accidentally, to make finds that make it possible to influence a specific mechanism." This deepening into molecular mechanisms has become a prerequisite for a new era in oncology — targeted therapy. According to Anatoly Makhson, in his youth at the institute, doctors knew that there was a disease called "breast cancer", and now there are about a dozen of its varieties that differ in mechanisms.

"Previously, we did not understand why a patient with stage three breast cancer can live for a long time, but dies with the first one," continues Mr. Mahson. — But because the tumors are different. There are very aggressive species." But aggressive ones also succumb when the appropriate key is selected for them. Anatoly Makhson tells how they managed to cure a woman with stage four lung cancer, with metastases in lymph nodes, liver, bones. Fortunately, the hospital has diagnostic equipment with which it is possible to detect known oncological mutations in genes. The patient was diagnosed with a mutation of the so-called ALK-positive non-small cell lung cancer. The discovery of changes in the ALK gene is still quite recent — 2007. Specifically for this target, Pfizer created the drug krizotinib, which literally immediately showed very good effectiveness, as a result of which it underwent accelerated clinical trials and was registered in the USA in 2011. And this year he appeared in Moscow. After treatment with crizotinib for two months, the examination showed complete remission. "We look at the pictures, and there is nothing there, everything is gone, and metastases too," says Anatoly Makhson. — And this is an amazing modern achievement"

According to Kirill Tversky, medical director of Pfizer in Russia, this is one of the first drugs for personalized therapy of non-small cell lung cancer. It acts only on the type of carcinoma that is characterized by the ALK mutation. "Such a mutation occurs in a small population of patients, from four to seven percent, with NSCLC, but it is in this group that the drug shows amazing results. Many patients included in clinical trials four years ago are alive, although they were given only months of life before that." The drug was awarded the Galen Prize, a kind of Nobel Prize in medicine

The first targeted and personalized drug in oncology is herceptin, which was created by Roche for the treatment of HER2-positive breast cancer, which occurs in 20-25% of cases. According to the medical director of Roche in Russia Rustam Galeev, after a year of therapy with this drug, seven out of ten patients with early stages had no signs of the disease even after ten years. Thanks to herceptin, more than a million patients around the world have fundamentally extended their lives

For more than 35 years, they could not find an effective treatment for a very aggressive skin disease — metastatic melanoma. "Only about 15 percent of patients responded to standard chemotherapy," says Rustam Galeev. — At the same time, the life expectancy did not exceed six months. But the saddest and most insulting thing is that this type of cancer often affects very young people. Of course, the melanoma drug was expected as a miracle." And when a mutation in the BRAF gene was discovered, Roche developed the drug vemurafenib, to which about 80% of patients responded in clinical trials. Last year, the drug was registered in Russia

More recently, Takeda's brentuximab vedotin was approved in Japan and Europe, and earlier in the United States, for the treatment of recurrent, or resistant, Hodgkin's lymphoma. This malignant disease was mostly well treated with standard chemo and radiation therapy, if it was diagnosed at the initial stages. But there were patients who received several courses of such therapy, then underwent bone marrow transplantation — the tumor stubbornly did not respond to treatment. Scientists still managed to find a specific target for which a new drug was created. 102 people who were actually sentenced to death took part in clinical trials. According to the company, 30% of patients had a complete recovery, 70% had a significant improvement or partial remission. The drug has seriously changed the life expectancy of such patients. While he was not in Russia, he was imported by the Gift of Life Foundation. The registration process is underway now.

It is known that a tumor is like an organism. She is also capable of evolution and is fighting for her existence. They shoot at her, but she finds tools so as not to die. Having deceived the medicine, the tumor begins to grow again. How happy scientists and doctors are, not to mention patients, when a new drug is being developed that seems to hit exactly the target! But it happens that after a while the medicine for some reason ceases to work, the tumor becomes resistant to it. "AstraZeneca has a wonderful drug for the treatment of non—small-cell lung cancer with a mutation of epidermal growth factor," says Vitaly Prutsky. — However, it was noticed that about a year after the start of therapy, a certain number of tumors acquire resistance to the drug. It turned out that this is facilitated by a new mutation that occurs in the same gene. The company aimed at it to create a new drug, which is currently undergoing the third phase of clinical trials."

It seems to turn out that the tumor is still ahead of scientists, they can only track its maneuvers and try to pick up a new weapon. According to Kirill Tversky, the near future is associated with highly targeted personalized therapy, molecules will be created that affect the specific mechanisms of functioning of various tumors. There are dozens of such targeted molecules, many of them are in the development of Roche, Novartis, AstraZeneca, Merck, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Bayer, Takeda, Boehringer Ingelheim; there are many projects of small biotech companies.

One of the rapidly developing areas in oncology is cancer immunotherapy. "The idea is not new," says Vitaly Prutsky, "twenty years ago we were taught in institutes that immunity fights and interferons should help, but then it turned out that everything is much more complicated. Many interesting discoveries have been made about the interaction of tumor cells and immunity. Now several companies in the world are conducting projects in this direction, including AstraZeneca. I think that immune therapy will be especially effective in combination with chemotherapy or targeted." One of these immune drugs is being developed at Roche. According to doctors from different countries participating in clinical trials, the new molecule shows very encouraging results, although at first there were many skeptics in medical circles. But when they saw with their own eyes the patients who had actually said goodbye to their relatives and "revived" as a result of testing a new molecule, they were inspired. According to Anatoly Makhson, the future of oncology is connected with the creation of personalized vaccines. According to him, they also show impressive results in research. By the way, such vaccines are also being actively developed in Russia — in the company "NewVak", the N. N. Blokhin Russian Cancer Research Center, the P. A. Herzen Moscow Research Institute of Oncology, the N. N. Petrov Research Institute of Oncology in St. Petersburg. In the latter, in particular, several vaccines have been created, one of which has already been registered and is used for treatment.

Statins and stents. The situation in cardiology has also changed significantly over the past two decades. "I will tell you two cases: one happened many years ago, when I worked in one of the district hospitals of Kazakhstan, and a relatively recent one," says RAMS Academician Rafael Oganov, chief researcher of the FSUE GNITS of Preventive Medicine of the Ministry of Health and Social Development of Russia. — A patient with angina was admitted to the district hospital. And everything seemed to be under control. But his daughter came to him and, apparently, they quarreled. I will never forget how right in front of my eyes he began to develop a myocardial infarction. I give him everything he needs—no effect. And two hours later he dies. Now, of course, everything would be different." And Oganov tells about a recent case. A large boss from the company next door was literally brought to the GNITS on his hands. The pressure is dropping, all gray, the pulse is barely palpable: "We quickly did an angiography for him, saw a thrombosis and immediately did stenting of the artery. Twenty years ago, he would most likely have died. And now the centers of high-tech medicine, which have all the necessary specialists and modern technologies, are saving people." 

Speaking about the achievements in cardiology, Raphael Oganov begins with prevention. I ask him to switch to pills and modern methods in surgery, but he gently says: it is still unknown what is more important. It sounds trivial, but numerous studies show that it acts on the possibility of reducing mortality from coronary heart disease. Quitting smoking — reduces by 35%, changing the wrong diet — by 45%, physical activity — by 25%, moderate alcohol consumption — by 20%. "About twenty years ago, a coherent system of risk prediction crystallized," Oganov continues. — It takes into account five factors: gender, age, cholesterol level, blood pressure and the fact of smoking. But we must understand that it predicts risks when a person still does not seem to have any manifestations of the disease. There are special computer programs that take into account all the total risks and make predictions." And the doctor gives recommendations on how to change the lifestyle and what medications to take proactively.

Many experts call the emergence of statins, cholesterol—lowering drugs, a revolution. And therefore, reducing the risk of developing atherosclerosis and in the future — serious cardiovascular diseases. "Before them, they could not cope with cholesterol," says Oganov. And although the first statins appeared in the late 1970s and early 1980s, their triumph was somewhat blurred by side effects. However, already in the 1990s, new generations of statins appeared. According to some reports, the prescription of these drugs in Europe increased fivefold from 1996 to 2001. Large-scale clinical studies have been conducted, which have shown that statins reduce the incidence of strokes and heart attacks by 30%, coronary mortality by more than 40%. "These medications not only prolong life, but also significantly improve its quality,— says Vitaly Prutsky. —We are proud that AstraZeneca has created one of the modern statins, which is now called the gold standard, because it shows amazing effectiveness in reducing low-density lipoprotein cholesterol, the so-called bad cholesterol."

According to Raphael Oganov, a number of drugs that control blood pressure have appeared. Previously, there were not very many of them, some of them had unpleasant side effects, and people simply stopped drinking them. Now there are drugs that act on specific mechanisms with a minimum of side effects and much greater effectiveness.

Many classes of drugs are undergoing a similar evolution. For decades, with atrial fibrillation, the whole world has used almost one anticoagulant — a drug that dilutes blood and prevents thrombosis, which is one of the main causes of strokes — warfarin. This is a really effective medicine, but, unfortunately, it has a number of restrictions when taken and requires constant monitoring. A certain concentration of the drug should be maintained in the blood of a patient taking warfarin. If there is less of it, the risk of thrombosis increases, more — it threatens with bleeding. "Over the past five years, four new oral coagulants have appeared in the world. Fifteen years ago, scientists became interested in how to create a drug that could replace warfarin," says Dmitry Vlasov, medical director of Bayer in Russia. — In terms of effectiveness in reducing the risk of strokes, new drugs are not inferior to warfarin, but at the same time they have significantly higher safety. Unlike warfarin, they are more convenient — they are combined with any products and other medications, which is very important for patients who take several medications. Another important advantage is that you do not need to constantly monitor the concentration of the drug in the blood." Bayer has developed an oral coagulant, which is taken only once a day. Today it is the most prescribed drug in the world of a new class of anticoagulants.

In Europe, up to 70% of the population drink statins as vitamins, take blood thinning drugs. Especially in adulthood, when the risk of developing cardiovascular complications increases. In our country, it often happens that people face a problem when it is already burning. They faint and fall on the table to surgeons for plaque removal or stenting, fall with a stroke or heart attack, where the result may not always be predictable. Strokes and heart attacks are our Russian catastrophe. Maybe that's why a few years ago the Ministry of Health decided to create high-tech care centers, where high-class specialists, the latest equipment for diagnosis and treatment are concentrated. "Now, if a patient has signs of serious cardiovascular disorders, he is taken to such a center," says Oganov. "And his chances of survival increase significantly, since his problems can be solved, in particular, with the help of modern endovascular technologies."

I had to observe how quickly and deftly such operations are done in the Bakulevsky center. Five minutes in one operating room, five minutes in the other was spent by the head of the Department of X-ray endovascular Diagnostics and Treatment of the Bakulev Scientific Center for Cardiovascular Surgery, Academician of the Russian Academy of Medical Sciences Bagrat Alekyan. A day later, patients can already go home and get to work. "In our country, 50-55 percent of patients die from heart and vascular diseases. Acute myocardial infarction or acute coronary syndrome is very common, which quickly leads to death. 20-25 percent of patients die, the remaining 75-80 percent become disabled,— Bagrat Alekyan says. — Thanks to new methods of X-ray endovascular surgery, acute myocardial infarction can be treated promptly. If we put a stent in quickly, we will prevent a heart attack."

The first stents often acted only temporarily, because the plaques managed to grow through them. But at the beginning of this century, they came up with a drug-coated stent that stops the growth of cholesterol plaques and their germination, a little later they came up with a biodegradable frame. "Like a metal stent, the frame developed by Abbot opens the lumen of a clogged vessel and restores blood flow to the heart, however, unlike a metal stent, the frame dissolves in the vessel after a while," says Sergey Antonov, head of the Abbott endovascular equipment division in Russia. — As a result, a potentially greater flexibility of the vessel is preserved. In addition, the frame allows us to significantly expand the possibilities of therapy, for which metal stents can become a limitation." Now this new product, which has recently been used in 60 countries around the world, is also available in Russia.

Bagrat Alekyan considers the aortic valve to be a fantastic development, which can be installed through a catheter without performing open-heart surgery. According to Alekyan, many more technologies have appeared in his field in recent years. For example, to reduce blood pressure, if no drugs work, it is possible with the help of radio radiation supplied by a catheter to the nerve endings and destroying these endings. After that, the pressure decreases by 30 mm. "Artificial pacemakers and implantable defibrillators have appeared," Raphael Oganov continues. — Sometimes sudden death is caused by sudden ventricular fibrillation. Now patients at high risk are hooked up with a defibrillator, which in case of an attack automatically gives a discharge, and fibrillation stops."

In 2010 , the number of pharmaceutical companies being developed
medicines for the treatment of various diseases amounted to:

From stroke, depression, drunkenness. Strokes are extremely common both in Russia and around the world. It was believed that after a stroke, a person definitely becomes disabled. But a better understanding of the disease allowed the use of innovative rehabilitation techniques. "Previously, people immediately after a stroke tried to turn in bed as little as possible and generally disturb," says Mikhail Piradov, Deputy Director for Research and head of the Department of Neuro—Resuscitation of the Scientific Center of Neurology, Corresponding member of the Russian Academy of Medical Sciences. — Now neurologists are already starting to activate the patient on the first day, no matter what condition he is in, even with severe strokes. In particular, we widely use robotic computerized systems in our center. If the arm or leg does not work, we put them in special devices that begin to develop them under the supervision of a specialist. At the same time, a person may even be in a coma. Studies show that early rehabilitation very effectively improves the quality of life after a stroke. Often a person is not only able to perform ordinary actions, but can also return to normal work if it is not associated with heavy physical exertion. We observed patients who were helped by robotic rehabilitation even two years after a stroke. But of course, it's better if it's done right away."

Professor Piradov says that in recent years a large number of innovative equipment has been developed to help neurologists, both diagnostic and therapeutic and rehabilitative: "The locomotive of progress in neurology, of course, has become computed tomography. It was first put into practice in the early 1970s. To date, many methods of tomographic diagnostics have appeared, which make it possible to detect certain changes in the brain at the earliest stages, for example, to see the focus of a stroke very clearly. And the faster and more accurate the diagnosis, the faster and more effective the treatment."

One of the most advanced treatment technologies has now become navigational transcranial noninvasive magnetic stimulation, which allows you to concentrate the strength of the magnetic field in the stroke-affected area with a diameter of only 2-3 mm, generate electrical impulses that, spreading through the nerves, are sometimes able to awaken seemingly hopelessly damaged brain structures.

"Another important achievement in the field of stroke treatment is hemicraniectomy,— says Mikhail Piradov. — In severe strokes, one of the frequent complications is cerebral edema, which often leads to death. The brain swells and swells. And the skull is holding him back. In adults, there is only one hole where the swollen brain can exit — the large occipital. But it is in this area that the respiratory and vasomotor centers are located. When the swollen brain literally pushes them into this hole and presses them against the walls, the patient dies from cardiac arrest or breathing." Now you can quickly remove part of the cranial box, let the brain go beyond it, and in a few weeks, when the brain returns to its normal size, put part of the cranial bone in place. This technique began to be practiced in the 1990s, but widely - since 2007. And she saved a lot of people.

As for medications used to prevent strokes, they are about the same as in the field of cardiology: lowering blood pressure, improving blood flow, lowering cholesterol levels. They are constantly being improved, becoming safer and more effective. "A relatively new trend, and I would say an old one revived at a new level, is a personalized approach to patients,— Mikhail Piradov continues. — For example, we are conducting a study that will allow us to understand why such a widespread drug for the prevention of cardiovascular complications as aspirin does not work on every person, but only on three out of four. With the help of special diagnostic test systems, we find out which tool will be most effective for each individual patient. After all, we are not treating a stroke, but a patient."

Among the diseases of the central nervous system, mental disorders are now rapidly becoming leaders. WHO compares their spread with a real epidemic. According to WHO estimates, about 350 million people suffer from depression worldwide, 150 million are disabled. They began to select therapy for her a long time ago. Since about the 1950s, the first antidepressants have been used. But as often happens, they were not effective for everyone and often had a lot of side effects. All this explains the ongoing attempts of scientists to create more effective drugs. The Lundbeck company, concentrating its developments in the field of the central nervous system, is now registering in Russia vorteoxetine, an innovative antidepressant with a multimodal mechanism of action that determines the presence of a whole complex of therapeutic effects. In addition to eliminating the symptoms of depression, the drug has a pronounced effect on cognitive symptoms (impaired concentration, memorization, memory, decision-making ability).

Alcohol dependence also belongs to the disorders of the central nervous system. It is clear that this is a serious problem for Russia. "According to official estimates, there are about two million such patients in our country, according to experts — up to 12 million," says Andrey Mukhin, medical manager of the Russian division of Lundbeck. — Traditionally, alcohol addiction is treated using the principle of complete abstinence from alcohol. Not every patient is ready to accept this condition. In this sense, our company has developed a unique drug nalmefene, which, being an inhibitor of opiate receptors, allows a person not to lose control when drinking and not to allow a breakdown. The main purpose of taking the drug is to significantly reduce the amount of alcohol consumed and, in this regard, reduce the risks of undesirable consequences: health disorders, conflicts, problems with the law. Subsequently, some patients may come to absolute sobriety. Since the patient himself decides to take the drug, his motivation plays a significant role. Essential assistance is provided by doctors who possess the latest motivational techniques."

Pfizer recently launched an innovative drug for nicotine addiction, which was also awarded the prestigious Galen Award. It was developed for ten years, along the way, scientists rejected about 30 thousand candidates for a new drug. But I was pleased with the result. When following the course, it helps nine out of ten smokers. And this means that someone has significantly reduced the risk of cancer. The acceleration of discoveries in the field of living systems also causes acceleration in the creation of new drugs, diagnostic systems and medical equipment. Multidisciplinary integration contributes a lot to this. Experts believe that in the coming decades, this acceleration will help introduce new means into medicine that will treat people and make their lives more dignified and active.

Portal "Eternal youth" http://vechnayamolodost.ru23.06.2014