Precision medicine: futurology or reality?

The process of discovering new treatments involves several phases, including clinical trials. Although the design and implementation of these trials have evolved over time, there is still response variability among participating individuals that is not fully explained by environmental, age, or nutritional factors. The studies surrounding the explanation for these different answers advanced with studies of the human genome. That's what a paper of the IPEA (Institute for Applied Economic Research).

Thus, pharmacogenetics emerged from the intersection between genetics, biochemistry, and pharmacology. This area, which is one of the foundations of precision medicine, investigates how genes interfere with the response to certain medications. In short, variations in the genetic sequence result in a variability in the response to medications. In addition, knowledge of genetic sequences and alterations provides useful data for prevention and direct medical intervention. This knowledge is translated as personalized medicine or precision medicine.

“Precision medicine, or personalized medicine, is the customization of medical treatment based on the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or in their response to a specific treatment” — is how you define a publishing of 2020 of the IPEA. In short, precision medicine unites data that are commonly used to diagnose and treat a patient, such as symptoms, family history, and complementary tests, with the individual's genetic profile.

According to a study From 2019 at the Federal University of Bahia (UFBA), around the 1980s, biomedicine underwent transformations as a result of advances in molecular biology, biotechnology, genomics and other innovations. “The cellularization of biomedicine is part of this process of technoscific transformation in which a new way of looking at and understanding the body at its molecular level comes to complement, if not supplementary, the traditional clinical view,” the study points out.

In the course of these advances, the name personalized medicine emerged in the late 1990s, marked by pharmacogenomics and the possibility of developing medicines aimed at the genetic characteristics of a specific population group. But this term of personalized medicine has been losing space in recent times for the concept of precision medicine, which gained prominence when it became associated with important genomic sequencing research projects in the United States and China.

The preference for the term “precision medicine” is related to a perception that medicine has always been personalized in clinical practice. In this sense, it is alleged that the designation “personalized medicine” can be misinterpreted, implying that it refers to the development of treatments and preventive measures exclusive to each individual, rather than approaches that apply to segments of the population.

Still, in addition to the name, the understanding of precision medicine is also expanding and its potential must consider some areas. Um paper From 2020, the IPEA notes: “From a treatment point of view, it allows the choice of drugs that minimize side effects and that produce the best results. From the perspective of prevention, it allows the detection of susceptibility to certain pathologies, even before they become clinically manifested, allowing their monitoring and even prevention. From an industry perspective, it allows the development of solutions for individuals or groups of patients who would not respond to conventional treatments and can potentially reduce the costs and delay of clinical trials.”

In an exclusive interview with Green Rock, Ricardo Di Lazzaro, doctor and co-founder of Genera, the first “direct-to-consumer” genetics laboratory in Brazil, explains that an individual's knowledge of their predispositions may lead them to changes in habits or even to specific indications about the use of medications.

“Knowing more about your genetic predispositions and risks is very relevant. This can range from lactose intolerance, in which you can simply change your habit and reduce the amount of milk to have less intestinal discomfort, to more complex conditions such as Leiden factor V, which indicates, for example, a very high risk of thrombosis, especially with the use of some hormonal treatments,” she says.

The basis of precision medicine: genetic testing

Genetic test results can be evaluated to anticipate individual predisposition to certain diseases based on the genetic profile. That is, they can predict a person's risk of developing certain diseases. In this sense, cell and gene therapies also fall within precision medicine, with current emphasis on conditions such as leukemia, degenerative retinal diseases, and lymphoma.

Beyond the scope of prevention, genetic tests allow an assessment of the response potential of a therapy, and are of paramount importance for precision medicine. When genetic data is cross-referenced with pharmaceutical and clinical information, researchers are able to identify patterns of efficacy and how genetic variations relate to those results. In this way, clinical trials can test these hypotheses, leading to the establishment of better clinical guidelines in the treatment of certain conditions.

According to the National Institutes of Health, in 2017, more than 50,000 genetic tests were available for about 10,000 different clinical conditions. One of the major foci is cancer, but there are tests aimed at identifying variations in enzymes associated with the metabolism of antidepressants, anticoagulants, and proton pump inhibitors.

Genome-editing gene therapy also gained strength starting in 2012 with the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) system, as indicated in the article “Precision medicine/personalized medicine: critical analysis of the transformational movements of biomedicine at the beginning of the 21st century”. This tool offers a way to correct genetic mutations in rare diseases and complex diseases, such as scissors that detect and cut pieces of DNA, ordering the genetic code.

The advancement of precision medicine in the world

Genetic testing and precision medicine have been advancing in the world, but at a different pace depending on each location. The United States stands out. According to OECD, in 2016 investment in precision medicine amounted to US$ 215 million, of which US$ 130 million was allocated to the National Institutes of Health (NIH) and US$ 70 million to the National Cancer Institute.

In the European context, it is worth mentioning the European Commission's “Personalized Medicine 2020 and Beyond” project, which aims to provide precision medicine to the population and promote the development of strategic research. European countries engage in studies focused on cancer and rare diseases. Among them, there is a highlight of investments in countries such as Germany and the United Kingdom.

In Brazil, on the other hand, there are advances, but also many gaps. Ricardo Di Lazzaro says that the greatest highlight in the country is in the area of Oncology. “Tumor treatment is indicated based on gene expression and tumor mutations. This is already used - not in such an accessible way - but it already exists as something available in Brazil,” she says.

On the other hand, he highlights some gaps: “In the United States, for example, hundreds of drugs already contain pharmacogenetic information in the package insert. For example, if you have such a genetic alteration, you should take a lower or higher dose of a particular medication. That's something that doesn't exist in Brazil. There is a lack of information, both in the package insert, which few medications have, and for the professionals themselves to use this data for a more personalized treatment”.

In addition, Di Lazzaro indicates that in addition to recent advances in oncological and rare disease treatments, the area of psychiatry is also seen as promising and has gained some strength in Brazil. “Psychiatry also uses certain genetic tests at some level of treatment indication. On the other hand, there are surveys out there that say that cardiology is an area that uses this a lot and here in Brazil it is not something much explored”, he adds.

The challenges of precision medicine

Although there is great potential and the advances in precision medicine in Brazil and in the world are perceptible, several challenges need to be overcome, from cost to accessibility and ethical and social issues. The technologies are expensive and there is a need for more investment in research and in the computerization of health systems, facilitating the integration and access to patient data. In addition, many of these important technologies in precision medicine are new and are not accessible to everyone. Still, there is a discussion about protecting the health information of study participants.

In the Brazilian context, the co-founder of Genera highlights two challenges: medical education and access. “Brazil is a poor country and genetic tests require greater purchasing power. Molecular tests end up being something more exclusive. Access is greater in developed countries. On the other hand, there is this issue of medical education. Most professionals do not have this knowledge and training in college. The genomic area was historically very separate from the medical area and this brought here a reflection that we still see today,” he says.

Another point to highlight is the population's lack of knowledge about precision medicine. In 2018, a public opinion survey conducted by Personalized Medicine Coalition among the North American population, it was found that more than 60% were unaware of this concept. Still, when people understand what it's about, there's generally a positive reception, but that's not apart from concern for the security of their data.

On this point, Di Lazzaro understands that there is a more intense discussion in the United States. “I understand the importance of care, genetic data is sensitive. At Genera, we follow the LGPD, and we take every care with data access and security. But personally, I am very much in favor of open data, especially when thinking about product development and research. I share my genetic data across multiple platforms and studies, but that's an individual decision. But I understand that even so, perhaps there is a slightly exacerbated concern in some senses,” he concludes.

The potential of a mixed country and investment in Brazil

Di Lazzaro also reflects on the importance of sequencing the Brazilian population in the context of the advancement of precision medicine. “The Brazilian population is mixed and has a relevant component of Africans and indigenous people. So, the development of genetic analysis abroad is often not translated in a perfect way in Brazil. It's not that it's not going to work, but it probably works a little worse,” he points out.

He explains that much of what is known about genetic factors for different diseases has been studied from populations of European ancestry. In other words, in a mixed population such as the Brazilian one, the results may differ. In this sense, when considering the advancement of precision medicine, the sequencing of the Brazilian population plays a very important role.

“We are moving forward. Genera today has the largest genomic database in Latin America. There are almost 300,000 people who have already taken the test with us and we have access to the data, being able to do research and product development based on this. Now, if we look at it in terms of scientific publications and international databases, no matter how much there is an effort by the scientific community to try to bring results from diverse populations, the analyses are proportionately more European”, he points out.

Still, he adds that this miscegenated component is an opportunity for unprecedented discoveries. Non-European genomes are still part of unexplored terrain. “Without sequencing our population, we lose the possibility of, as a country, developing products that work much better for our own population,” he adds.

It is worth noting that in addition to private initiatives surrounding precision medicine, the public sector has also announced investments in the area. Genomic science and technology have been gradually incorporated into medical research. In 2015, the Brazilian Initiative on Precision Medicine (BIPMed) was launched in São Paulo, an initiative that brought together research centers focusing on the implementation of precision medicine in the country.

In addition, genetic tests in Brazil include the genotyping of up to one million polymorphisms and the complete sequencing of the exome. These options are intended to identify disease-related genetic mutations, assess genetic susceptibilities, and provide data on personalized treatments for a variety of medications.

Already in August of this year, The Ministry of Health announced that it will invest R$ 100 million in research on Precision Health with the objective of stimulating the country's scientific and technological development in the area. The action will invest in projects that must take into account applicability in the Unified Health System (SUS) and is part of the National Genomics and Precision Health Program — Genomas Brazil.