Sanctions hit Russians with orphan diseases

Diseases begin to be detected before birth

Today, at least 8 thousand orphan diseases are known in the world, however, if we combine all those who have been diagnosed with them, we get a rather impressive army of patients. 80% of genetic diseases are rare, and 50% of those suffering from them are children. Only a few people per million may suffer from this group of diseases, but if you collect all patients with rare diseases, it turns out that they are at least 3% of the population.

A flurry of rare diseases hit the world out of nowhere. In fact, they have always been – they just did not know how to diagnose. For example, a quarter of a century ago, doctors were sure that there was only one autoimmune bullous skin disease in the world. Today, ten of them are known. The genetically determined Fabry disease, which affects 1 in 40,000 people, was previously mistaken for atherosclerosis. However, accurate genetic screening has emerged, and now doctors know that this is a completely different disease.

The development of molecular and genetic diagnostics over the past 15 years has identified the causes of more than 300 diseases, more than 2.5 thousand disorders and syndromes. In many cases, early diagnosis of orphan diseases (that is, prenatal in the womb or neonatal at birth) can significantly improve the patient’s life. Of course, there is no point in examining all newborns at once for all 8,000 diseases. However, sometimes early detection helps to avoid tragedies, and in very simple ways. So, there are hereditary pathologies that are treated with just a diet, vitamins or cheap medicines.

The good news is that from January 1, 2023, a program of expanded neonatal screening for hereditary and congenital diseases will start operating in Russia. As the professor, president of the Federal State Budgetary Institution “National Medical Research Center for Pediatric Hematology, Oncology and Immunology named after N.N. Dmitry Rogachev” of the Russian Ministry of Health Alexander Rumyantsev, the list of tested nosologies will grow from 5 to 36 diseases.

The chief geneticist of the Astrakhan region, Irina Suprunova, notes that they are morally ready for the introduction of such screening, but there are not enough geneticists in Russia. Chief pediatrician of Children’s City Clinical Hospital No. 9 named after Speransky, professor, chief freelance immunologist-allergist of the Ministry of Health of the Moscow Region Andrey Prodeus, says that it is not yet entirely clear what to do with children who have been identified: “Screening and diagnosis are not an end in themselves. The main goal is to help patients, so there must be a logistics system. We will cope with screening, and what’s next is not very clear yet. Each identified child should be provided with an outpatient department for observation; a laboratory service is needed to monitor the condition of patients. It should be possible to help patients with a difficult diagnosis, they are usually brushed aside in every possible way. And it is also necessary to ensure the correct maintenance of dynamic registers. And yet, what has been done, an incredible breakthrough, we will find serious conditions at the preclinical stage.”

And it is also very important that serious problems can arise with the drug supply of such patients. More precisely, already existing problems can be significantly aggravated against the backdrop of supply disruptions due to the imposition of sanctions.

“My life turned upside down”

“One person in a million – millions for one person”: the conference of patients with orphan diseases “Rare Heat”, which takes place annually in Astrakhan, this year was held under this motto. More than 50 “rare” patients and “rare” doctors from the federal centers and regions of the country, patient organizations from Belarus, Kazakhstan and Uzbekistan, politicians, public figures gathered to once again draw attention to the problems of people with rare diseases. And leading experts in the field of rare diseases discussed the latest achievements in the field of their treatment.

Each patient’s story is heartbreaking. Elena Balabanova, beautiful, clever, sportswoman, mother of a boy with phenylketonuria. In this genetically determined disease, the metabolism of amino acids, mainly phenylalanine, is disturbed. And the main treatment is a low-protein diet. If it is not observed, the enzyme phenylalanine and its toxic products will accumulate in the body, which will cause severe damage to the central nervous system, manifested, in particular, in the form of mental retardation. Yet phenylketonuria is one of the few hereditary diseases that can be successfully treated.

“My grandparents are professional athletes: my grandmother is a skiing champion, my mother is the captain of a basketball team. In general, I come from a healthy sports family. She graduated from two universities and gave birth to a son. But at the age of 31, my life turned upside down: I learned from doctors that my child will never be able to eat anything except fruits and vegetables, because he has a very rare disease, and disability needs to be registered. Denial, anger – I lived through these stages for three years. Yes, it is very difficult to live with a child with special needs, but thanks to the support of doctors and parents of such patients, we become stronger. Today my son is ten years old, he studies in a regular school. To support him, I refused meat and other products that he cannot. He takes medicine three times a day, donates blood once a week,” says Elena.

Mom Natalia from Tyumen tells a dramatic story. When her son Roma was 4 years old, he was diagnosed with blood cancer – lymphoma. “Roma was born in 2012, this is my first child, and two years later my second son Maxim was born. And just before the new year, 2015, when Maxim was a year old, he fell ill with SARS, his condition worsened, and he was taken to the hospital. On December 31, I was told that my second son most likely has leukemia. We celebrated the New Year in silence. Then the diagnosis was not confirmed, but on January 4, Maxim was taken to intensive care, and on January 5 he died. Two months later, Roma began to get sick: kindergarten teachers told me that he often goes to the bedroom, he is left alone, his stomach and head hurt. We went to the doctors, who diagnosed him with appendicitis and scheduled an operation. He was operated on for 6 hours: a tumor 10 centimeters in diameter was found in his stomach. And they also cut out a part of the intestine with perforation. After that, he was prescribed chemotherapy. In 2017, a healthy boy, Kirill, was born to me, and nothing foreshadowed trouble, but again on New Year’s Eve he had a fever, and he spent 5 days in resuscitation. Everything repeated as with Maxim, Kirill died. We got a good doctor. Cyril’s condition was not alarming (temperature, raids in the throat), but she was alarmed by the fact that one of my children had already died, and the second had oncology. She suspected that Roma had something wrong with his immune system and sent him to the federal center. They confirmed the diagnosis – primary immunodeficiency, and performed an urgent bone marrow transplant. I don’t want other parents to go through the same thing as us,” says Natalia.

Primary immunodeficiencies (PID) are the most numerous group of severe genetic diseases (there are more than 400 of them) caused by a violation of one or more immune defense mechanisms. They occur in approximately one patient per 10,000 people, but their actual prevalence can reach a ratio of 1:500. According to experts, there are at least 7 thousand people with PID in Russia, the annual increase is about 180 people a year. According to leading Russian immunologists, 90 percent of children with primary immunodeficiency in Russia die undiagnosed. Children are often misdiagnosed and many, especially infants with severe immunodeficiency, die between 2 and 4 months of age.

“The birth of a sick child in a family is always a misfortune,” says Anton Emelin. – When I was little, I asked my parents for a sister or brother. And when I was 10 years old, my brother was born, who was constantly sick, suffered from bleeding. He was diagnosed with PID. And his life turned into a fight for drugs. Every misfortune with a person happens for something. Life brought me together with good people – doctors, other patients. We have created a society to help such patients. I am a lawyer, I try to help everyone, and today the provision of medicines is improving. Today, people with such a diagnosis can count on financial support from the foundation created on behalf of the president, and from 2023, every newborn will be diagnosed. It is extremely important to identify PID from the first days of life and prescribe treatment in time – then people have a chance for a full life.”

Previously, children with neuronal ceroid lipofuscinosis type 2 died in severe agony at 9–12 years of age. In this genetically determined disease, the bones break, due to the pathology of collagen, a pathological accumulation of a toxic pigment, lipofuscin, occurs in the brain. First, children lose coordination, then they stop talking, walking, and then they die painfully. Treatment was not available.

But today we managed to establish this process of medical supply. For example, 6-year-old Lera Zmeykova receives neuroinfusions of a modern drug (it is delivered directly to the brain). Previously, a terrible fate would have awaited the child, but in 2019 a medicine was invented, and Lera became the first patient. During treatment, the child has almost no seizures.

Introduce sanctions to ban the supply of drugs

Only 5% of rare diseases have a cure today. Alas, the cost of treating such patients can often nullify the budget of an entire locality, and yet in recent years the situation has begun to gradually improve, but only a small number of these diseases in Russia are included in state programs that allow patients to be provided with medicines for free.

According to Leonid Ogul, Deputy Chairman of the Committee for Health Protection of the State Duma of the Russian Federation, 20 years ago no one really knew about the existence of orphan patients, they were not given so much attention, there were no funds, there was practically no drug provision: “But there is not enough money from the funds, to provide drugs for everyone, so federal funding is needed. We have created an expert council on orphan diseases, and our goal is to transfer funding for all patients to the federal budget, not a single regional budget will pull them. There are no fewer of them, no one can predict their number. And we also need a government program and a state order for the production of expensive drugs in Russia – our manufacturers have every opportunity to produce them in our country.” Deputy Ogul sincerely believes that the Russian industry is able to overpower the production of such drugs in the country, besides, he is not very interested in international patent law, which prohibits the reproduction of original drugs before the expiration of patent protection (there are practically no orphan drugs that have already run out of patent protection) . “Yes, there is patent law, but when it comes to our children, everything is justified,” he says.

Patient organizations, meanwhile, look at life much more soberly and do not call on Russian manufacturers to violate international law. Anastasia Tatarnikova, chairman of the Rare House Association of Patient Organizations with Orphan Diseases, and Roman Mironov, a public expert in the field of organizing medical care and providing medical care to rare patients, made an open appeal to develop international documents prohibiting the imposition of sanctions on the provision of medical care and the supply of medicines. Surprisingly, there is still no such legislative prohibition in the world. “Due to the imposition of sanctions, we are increasingly thinking about tomorrow, because most orphan drugs are foreign,” says Anastasia Tatarnikova. – We found out that today there is not a single international document that would prohibit the imposition of sanctions on the supply of medicines, and there are already precedents when companies refuse to import certain medicines to our market. There are no guarantees at all that the sanctions will not affect the healthcare sector. In our country, a system of assistance to orphan patients has been built for many years, but relations between states are changing, and the cost of disrupting the supply of medicines is the patient’s life. Today, we live in a constant risk of interruption and delay in deliveries, this is a matter of concern for parents and patients. And there are no international rules prohibiting the imposition of sanctions in this area, so we urge them to be developed.”