Genomics against orphan diseases

Predict and win

Ilya Nosyrev, "Russian Planet"

The MIPT Center for Living Systems is one of the most advanced biotechnological research centers in Russia: developments are underway here for the diagnosis and treatment of diseases that medicine is not yet able to cope with. Among them, the so–called orphan diseases (from the English orphan – orphan) are rare ailments that are caused by mutations in the genome (the genome is a set of hereditary material enclosed in an organism cell. – RP.). They are incurable, and people with such mutations have to resort to special therapy all their lives, including medications and medical procedures. However, a lot depends on early and correct diagnosis here: if the disease is not correctly identified in time, a person may die. Among such diseases, for example, cystic fibrosis, in which congenital defects in the functioning of the glands of external secretion provoke severe disorders in the lungs and gastrointestinal tract. If you make a diagnosis on time, you can reduce the manifestations of a number of diseases to a minimum.

Diagnosis of these diseases in itself was expensive and difficult until recently, but everything is changing right before our eyes. "Our transcriptome sequencing and mathematical modeling laboratory, commissioned by the Ministry of Industry and Trade, has developed test systems that allow diagnosing diseases based on genome features," says Kamil Hafizov, a researcher at the laboratory of the MIPT Genomic Center for Living Systems. The system, created under a two-year contract that only recently ended, allows you to check mutations on a list of 60 diseases. "There is no need to read the entire genome, which is long and expensive – it is enough just to read only those parts of it where specific mutations are present. It's much cheaper and faster," says Hafizov. And most importantly, the patient does not even need to come here: doctors from all over Russia send only samples (saliva or blood) of patients. The laboratory assistant extracts DNA from the samples and loads it into a device that can read about 200 sections of the genome at one time. The test results are uploaded to the computer, then a report is generated based on them, which is sent to the doctor by e-mail.

Thanks to the careful selection of small (about 200 nucleotide bases) DNA fragments containing positions where pathogenic mutations occur most frequently, the Orphagen diagnostic system has significantly reduced the cost of genetic diagnosis and accelerated the process itself, allowing up to 2,000 mutations in 61 human genes responsible for 60 hereditary diseases to be detected. Such test systems have become possible in the last 2-3 years, when devices capable of quickly reading individual sections of the genome appeared. In general, they are among the tools available to the so–called postgenomic medicine - a branch of medicine that uses the results of genome research of specific patients. "In the list of diseases for which we diagnose, there are more common ones: cystic fibrosis, phenylketonuria, Fabry syndrome, Crohn's disease – and there are also those that occur infrequently," explains Hafizov. Previously, PCR analysis was performed for each mutation (Polymerase chain reaction is a research method that allows increasing small concentrations of certain DNA fragments in the samples under study. – RP.), which was expensive and took a lot of time. Thanks to new technologies, it is now possible to view several dozen mutations that are associated with this disease at once.

Of course, all these ailments are incurable, but it is possible to carry out substitution therapy for patients, maintaining a certain standard of living. "These diseases are quite rare, and pharmaceutical companies are not interested in conducting research for a small audience," explains Kamil Hafizov. – If they do such research, then it's all very expensive. In other words, this can be done either by the state or by such scientific centers as ours. There is not much commercial benefit from our activities – there are not so many patients, but the main thing is that it at least pays for itself." Some of the reagents are imported, and work is underway to replace them with cheaper domestic analogues. The devices themselves for reading sections of the genome cost millions of rubles, and there is no tendency to reduce their cost: again, their manufacturers are not interested in this.

The peculiarity of the technology is that it would be more profitable for the center to put it on stream: the fact is that the cost of each analysis depends on exactly how many samples are tested for each reception. It costs about 50 thousand rubles, but for this amount you can test both a sample of one patient and fifty, thus dividing the cost by the number of patients. Of course, the task of collecting so many samples is still difficult – frozen blood can be stored for a long time, but it is in the interests of the patients themselves to diagnose as quickly as possible. And there is no flow of patients yet: many doctors are not morally ready for new methods, they prefer to work the old-fashioned way. And this is despite the fact that there are very few similar diagnostic technologies in the world so far.

On average, one or another orphan disease occurs in about every thirtieth inhabitant of the Earth. On the one hand, not much, on the other – the total number of people affected by such ailments is estimated in the hundreds of millions of people. In total, more than 7 thousand such diseases are known . In Russia, about 15 thousand people suffer from such hereditary ailments, of which 6 thousand are children. The laboratory where Kamil Hafizov works compiled its list based on three main parameters. First of all, they chose diseases that are common in Russia: after all, different mutations occur with different frequency in different populations. All publicly available mutation databases are American, and when work began on compiling the list, it turned out that almost most mutations in these databases are almost not found in Russians. Secondly, they choose the most studied diseases with an understandable mechanism of development, so that it is clear which mutation leads to what consequences. Finally, such diseases were selected in which the patient can be helped: it makes no sense to diagnose a hereditary disease if, according to doctors, the patient's days are numbered. In the future, the list may increase by dozens of other ailments. "Our list of diseases can be expanded," says Kamil Hafizov. "Technically, it's not very difficult: a programmer needs about half a day to change the database, plus technical work to change the DNA sections that the device reads."

According to the scientist, the approach, in the development of which his laboratory participates, in the future can change the very system of treatment of diseases. The current medicine, which seeks to treat everyone with the same medicines, will be replaced by personalized medicine, which will treat any disease depending on the characteristics of the patient's genome. Of course, this revolution is unprofitable for large pharmaceutical companies, but now other companies are actively appearing that build their business on providing personalized services. This means that over time, it will become increasingly difficult for large companies to sell the same medicine to all sufferers.

Post-genomic medicine will also affect other areas of life, for example, family planning. All orphan diseases are laid down by recessive genes, that is, genes whose expression is suppressed if the paired genome in the genome turns out to be dominant. However, if the patient is unlucky and he got both paired genes with a harmful mutation from his parents, he will certainly develop the disease inherent in this mutation. "This means that the tests can be used for family planning – after studying the samples of a married couple, we will be able to tell her with what probability they may have a child who is susceptible to this or that ailment," says Hafizov.

The MIPT Center for Living Systems has other projects that are engaged in the development of other areas of postgenomic research. One is devoted to the study of the genome of somatic cells, on the basis of which it would be possible to build a reliable system for diagnosing certain forms of cancer. Another laboratory is engaged in historical genetics – it allows, for example, to determine for each person who applied for services, where his ancestors come from, to which ethnic groups they may belong.

In the near future, post–genomic technologies will be able not only to diagnose ailments, but also to prevent some of them in time – for example, studying the human genome in early childhood will determine whether he has a predisposition to the development of type II diabetes, hypertension or obesity - and avoid the development of these syndromes with the help of a proper lifestyle. Many of the rare diseases, if they are detected in childhood, can be cured: with proper therapy, they may not manifest themselves in any way throughout the patient's life.

"Projects related to the genetics of sports are also actively developing now: based on the study of a child's genome, researchers can tell parents which kind of sport he will have the best physical abilities,– says Hafizov. – Of course, while such tests are not the cheapest, and the average man in the street is not ready to give a thousand dollars for no clear reason." According to him, scientists still have to conduct a lot of research so that such analyses become truly useful. And yet the results of this work are not far off – the XXI century, without any doubt, will become the century of post-genomic medicine.

Portal "Eternal youth" http://vechnayamolodost.ru10.06.2015