Hereditary diseases of Russia
Edited cells normalize the work of the body
Valeria Nodelman, Izvestia
Five percent of the Russian population suffers from genetic diseases, but in some regions there is an acute situation. In Chechnya, the incidence of tyrosinemia type I (leads to cancer and cirrhosis of the liver) is 10 times higher than the world, in Dagestan, mucopolysaccharidosis type IV (severe skeletal deformity) is 15 times more common than in the world, in Chuvashia there is a high frequency of hereditary osteopetrosis (marble disease). The Ministry of Health believes that it is necessary to expand neonatal screening throughout the country for another 29 pathologies. Sergey Kutsev, director of the Medical and Genetic Research Center of the Ministry of Health, chief geneticist of the country, told Izvestia in an interview about why there is an increase in genetic diseases and what measures need to be taken in this situation.
Risk group
– How uniform is the prevalence of rare genetic diseases in the regions of Russia?
– The research of the Medical and Genetic Research Center has revealed in some regions a significantly higher incidence of diseases than in other subjects or even in the world. For example, in Yakutia, the frequency of type I spinocerebellar ataxia is quite high. Hereditary osteopetrosis is more common in Chuvashia.
Last year we conducted a study and found that in the Chechen Republic there is a significantly higher incidence of tyrosinemia type I – one case per 15 thousand newborns. While in the world this disease is much less common: one case per 100-150 thousand newborns. In the Republic of Dagestan, the frequency of type IV mucopolysaccharidosis is one case per 20 thousand infants. And in the world – one case per 300 thousand newborns.
We are exploring different regions of Russia step by step. It is very important to understand what kind of medical and genetic counseling they need, what measures regional ministries of health should take. Centers for the prevention and treatment of hereditary osteopetrosis with the help of bone marrow transplantation have been functioning in Chuvashia for a long time. The earlier the transplant was done, the more effective it is.
– What measures will you propose in Chechnya and Dagestan in connection with the revealed frequency of pathology?
– We believe that in Chechnya, it is absolutely necessary to expand neonatal screening, and by 10 nosologies at once. Because it can be done with a single analysis without additional costs.
In Dagestan, selective screening is needed (in risk groups). Doctors should be wary of mucopolysaccharidosis, know it well and diagnose it in time so that an enzyme replacement drug can be prescribed as early as possible.
– At what stage is this initiative of yours?
– So far at the level of the proposal to the Ministry of Health of Dagestan. I'm going to visit the region in the near future. We will try to establish cooperation between federal institutions and regional authorities. But the decision remains with the authority of the subject.
– What is the cause of these diseases?
– Tyrosinemia and mucopolysaccharidosis of type IV are inherited diseases. They appear when two carriers of a mutant gene marry, the risk is 25%. The reason is the high frequency of carrying mutant alleles that have accumulated in the population. It's not always about closely related marriages.
Check everyone
– Will you recommend introducing additional screenings at the federal level?
– Without a doubt, we need to expand neonatal screening, as in European countries. There, newborn screening is carried out not for five diseases, as in Russia, but for more than 30.
It has long been estimated that the benefits of early detection outweigh the costs. If we did not start treating the child in time, he will become disabled. Most often orphan (rare. – "Izvestia") diseases lead to deep disability. And the costs of the state for the maintenance of a disabled person are much higher than for preventive treatment.
– Does screening need to be expanded to 30 nosologies?
– We calculated that additionally, in addition to those for which we are already screening, we need to check for another 29 diseases. In 2017, the President of Russia was instructed to consider the possibility of expanding neonatal screening. The Ministry of Health has prepared such a proposal, but, as far as I know, it has not been agreed by the Ministry of Finance and the Ministry of Economic Development. Everything stopped there.
– Why are there more such diseases in Russia?
– The frequency of hereditary and congenital diseases has been increasing in recent years, but this is due to the development of diagnostic capabilities. A few years ago, a new generation sequencing technology appeared, which allows for genome-wide studies. They help to identify the disease where we have not seen it before. For example, we already believe that not 10%, but 15% of oncological diseases are inherited. And so for many groups of diseases.
The most important thing is that we detect new changes in the genetic apparatus and check whether they are really pathogenic. This is a task for the next decade.
Cellular editing
– What diseases can be cured by editing the genome?
– We have made significant progress in genome editing in cystic fibrosis. A very good result was obtained – about 10% of the cells can be edited. It seems that it is not enough, but it is the best result in the world.
In the future, we will be able to receive cells from the patient – for example, skin fibroblasts – transform them into pluripotent (capable of implementing several options for further development) stem cells, correct a genetic defect and then transplant them back to the patient. Edited cells normalize the work of the body.
In the future, it will be possible to treat other hereditary diseases and oncological diseases with gene editing. Genetic treatment of infectious diseases is also possible.
– Which of the new developments are already on the way?
– For oncological diseases, CAR technology has already been introduced in the world: chimeric antigen receptor, when lymphocyte receptors are changed so that they can recognize specific tumor cells. Drugs for the treatment of hemophilia, phenylketonuria, mucopolysaccharidoses are at the stage of the second and third phases of clinical trials.
– And what developments are being carried out at your center?
– We continue to work on Landuzi-Dejerin myopathy while preclinical studies, laboratory stage are underway. A drug has been developed for the treatment of colorectal cancer – the preclinical has been completed, now they should move to the stage of the first phase of clinical trials.
– How much importance does the state attach to the work of the medical and genetic service now?
– In 2018, the state expanded the program of financing drugs for the treatment of rare diseases at the expense of the federal budget – "Seven Nosologies" – by five names. This is a lot of attention to the problem, not all European countries can afford it. And yet the role of the medical and genetic service has not yet been fully evaluated by the state.
This year we celebrate 50 years since its foundation. Now in most regions there are medical and genetic consultations, but in four (Ingushetia, Yamalo-Nenets and Chukotka Autonomous Districts, in the Jewish Autonomous Region) they are still missing. The complexity of the organization of medical and genetic services in these subjects is understandable. But it is unclear, for example, the decision of the Ministry of Health of the Murmansk region on the reorganization of the medical and genetic department, as a result of which a fully functioning division of the regional hospital will cease to exist.
There are only 270 geneticists working in the regions - about one geneticist for more than half a million people. And the need for such specialists is at least twice as great.
After all, they are needed because the number of hereditary diseases is constantly increasing. For example, we now know almost a thousand genes that cause the hereditary form of epilepsy. These forms need to be diagnosed, treated, and prevented in specific families. All this should be solved by the medical and genetic service. So far, such issues are solved only by the Medical and Genetic Research Center. Although in total, about 5% of the population suffers from genetic pathologies – this is a lot. More than 7 million people.
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