On the threshold of gene therapy

Catherine Braunstein: "We are on the verge of introducing sequencing into everyday medicine"

Kristina Firsova, IF24

In the last decade of the last century, large-scale international research projects in the field of genetics and molecular biology began to be implemented. The results obtained by scientists allowed a new approach to the diagnosis of hereditary and rare diseases. The use of human genome sequencing – the description of the DNA nucleotide sequence – provides doctors with the opportunity to make the most accurate diagnosis and prescribe optimal treatment to patients. Catherine Braunstein, M.D., Ph.D., associate professor at Harvard Medical School and scientific director of the Manhattan Orphan Diseases Research Center, talks about the prospects of gene therapy. 

Gene technologies: better, faster, more accessible

– The Human Genome project started in 1990, and the research was completed only in 2003. How has gene therapy changed since then?

– We are on the verge of introducing sequencing technologies into everyday medical practice. First of all, they have become much cheaper and more accessible for mass use. The Human Genome project made it possible to determine individual sequences of gene chains in humans for therapeutic purposes. This has led to a real revolution in diagnostics and the emergence of new principles for prescribing treatment.

In 2010, a large-scale continuation of the successful Human Genome project was launched. Scientists from the USA, Russia, South Korea, Canada, Iran and Sweden have joined forces to study blood proteins, the central nervous system and the liver. The initiative was called the "Human Proteome". In the early 2010s, new generation sequencing (NGS) was developed. Thanks to the beginning of their use, it was possible to obtain the final result of the analysis less than 100 days after the biopsy. Scientists were able to set up previously technically impossible experiments. The study of chromatin and trascritome has begun. Research in the field of cellular and molecular biology has reached new heights.

– In 2016, the market for gene drugs was estimated at more than $500 million. It is planned that by 2023 the figure will exceed 4 billion. What do you think about this? Won't gene therapy just become another way of making money?

– There is nothing wrong with the fact that pharmaceutical companies receive additional income by introducing new technologies. New drugs are becoming cheaper and therefore more affordable. Their assortment is constantly expanding and efficiency is increasing. Time shows that gene therapy is getting cheaper every year. In addition to improving the effectiveness of the treatment of many diseases, among the positive aspects of the expansion of the market for gene medicines can be called a constant increase in funding for scientific medical research by pharmaceutical concerns.

– For several years you have been developing sequencing and pharmacogenomics programs. What news do we expect in this area? Are there any new developments?

– Until 2011, I participated in several startups united by the Health 2.0 program. After starting work at the Boston Children's Hospital, I participated in several laboratory research projects carried out by the Manhattan Orphan Disease Research Center.

These are the programs "Child psychoses", "Orphan and rare diseases", Vivily. Participation in the first of them made it possible to better understand the genetic prerequisites for the appearance and development of mental disorders in very young children. We have identified a link between the regulation of phosphates in the body and the genetic causes of mental retardation. The second project is dedicated to identifying the relationship between heredity and chronic disorders, hypersensitivity or immunity to pain. Vivily is a major project that is carried out under the patronage of one of the leading research centers in the field of digital and molecular biology and genetics – the Getty Lab. The program deals with the evaluation of experiments in real time, which allows laboratories to maximize productivity with minimal time and resources. Thanks to Vivily, the possibilities of conducting individual experiments for each patient in need open up.

The future belongs to genomics

– A person has about 20,000 genes, and this greatly complicates the definition of certain diseases. What does collecting genetic materials do in general?

– It is necessary to create an effective database in which it would be easy to find any possible combination of about 20,000 genes that are responsible for the vital activity of each individual inhabitant of the planet. The only problem of its implementation is the protection of personal information. I think it's not worth putting personal data above health. The preservation of anonymity does not allow later identification of the genetic material stored in the database, if necessary. If someone is seriously ill, as a rule, the protection of personal information becomes not as important for him as for a healthy person.

– In China, the creation of a DNA center is at the last stage, where it is planned to store genetic samples of 80 million citizens. What will this DNA center do? Is it possible to build similar institutions in other countries?

– As part of the implementation of the state program for the development of healthcare in China, a National DNA Research Center is being created. Its creation will cost the Chinese budget $900 million, according to 2017 estimates. It is planned that the new institution will conduct large-scale studies of cognitive processes and human brain activity in the early stages of development, the search for new methods of treating cancer, rare and chronic diseases. One of the priority areas will be population genetics. The center will collect and store DNA samples and other genetic material of more than 80 million residents China.

– Now a new method of genome sequencing is widely used. How accurate is the data it shows? Are errors excluded?

– The most common and frequently used method is exome sequencing. When using it, only a small part is analyzed – about 1% of the human genome. Based on the data obtained, a conclusion is made about the condition of the subject. However, when we study not the whole genome, but only a small part of it, our conclusions cannot be absolutely accurate. It is impossible to exclude errors. Some percentage of inaccuracies always remains. There are also some things that we cannot see, even after examining the material 100%, for example, an epigenome. We cannot claim that sequencing is the last word in gene research. The final decoding of the genome is a matter of the future. Nevertheless, sequencing is a step towards getting answers to all the questions that genomics poses to us.

Gene therapy is becoming a common practice

– More and more children with rare genetic diseases are being born now. Statistics show that about 30% do not live up to 5 years. Does genetic analysis allow to determine the presence of such diseases in the early stages of pregnancy?

– Such studies are done in many medical institutions in the USA and abroad. For example, in the Children's Hospital of Boston, a child is scanned, on the basis of which they come to a conclusion about the presence or absence of any problems and pathologies. A multi-faceted examination of the embryo makes it possible to successfully diagnose various diseases, including those caused by genetics.

Already at the stage of "family planning", it became possible to exclude the possibility of the occurrence and development of serious diseases in children that are common in their family. It is possible to correct the development of the organism at the gene level and eliminate threats. It is quite possible to prevent pathology before it appeared these days.

While sequencing my own genes, the first thing I noticed after receiving the results was whether there was a chance of getting amyotrophic sclerosis. This disease leads to paralysis and cerebral infarction. The probability of its development directly indicates the possible life expectancy of a person.

– Previously, many doctors were very skeptical about such a diagnostic method as gene analysis. Why did this happen? And how has the situation changed today?

– Skepticism causes everything new. It's natural. People are wary of what has not yet been confirmed in practice. Many doctors simply could not immediately take seriously the diagnoses made on the basis of the analysis of gene chains. Some are wary of such diagnostics to this day. I think it's temporary. New methods always replace the old ones.

– Gene therapy and genetics are developing very rapidly now. What do you think the future holds for us in this area?

– I think genetics in the future will allow detecting diseases much earlier than now. There will be opportunities to detect most pathologies even before they manifest themselves, and successfully treat them with the help of gene therapy. For example, we will find out under what conditions a virus showing a lack of protein can be placed in the body. Of course, it is impossible to be sure that this technique will become universal, but, undoubtedly, it will significantly expand the use of gene therapy.

Portal "Eternal youth" http://vechnayamolodost.ru