Latvian Council of Science funded Fundamental and Applied Research program project "Tuberculosis treatment: exploring the perspectives for personalised therapy" implemented by Rīga Stradiņš University in collaboration with the Latvian Biomedical Research and Study Centre and the Latvian Institute of Organic Synthesis, is essential for advancing towards personalized tuberculosis treatment. This is vital given the disease's significant socio-economic burden. Lead researcher Dr. Renāte Ranka, now a Tenured Professor at Rīga Stradiņš University, explains that the study generated new knowledge and developed novel methodological solutions, which could have a broad impact on advancing individualized approaches to tuberculosis therapy.
Tuberculosis – An Ongoing Battle
Tuberculosis (TB) is one of the most devastating infectious diseases that has threatened humanity for centuries. While modern medicine has made significant strides in treating it, TB remains one of the deadliest infectious diseases worldwide. It can affect anyone – regardless of age, location, or social status. Many mistakenly believe TB won't affect them, but the harsh reality is that no one is entirely immune.
The Personalized Therapy Approach
Prof. Renāte Ranka explains that TB treatment involves more than just taking medications – it is often a tough battle for survival requiring persistence and time. Standard therapy for drug-sensitive TB lasts six months, during which patients must take multiple medications simultaneously. However, not everyone responds to standard treatment the same way. Some recover quickly, while others suffer severe side effects or even life-threatening complications. Scientists work tirelessly to understand these differences, searching for specific biomarkers to predict treatment outcomes and tailor therapies to individual patients. Personalized medicine isn't a distant future – it is a chance to reduce treatment failures today.
Genes That Determine Drug Fate in the Body
Why do drugs work for one person but not another, or even cause severe side effects? The answer lies partly in our genes. Pharmacogenetics studies how genetic differences affect drug action and treatment effectiveness. Some patients’ enzymes metabolize drugs as expected, while others’ enzymes may be altered, causing drugs to accumulate and become toxic. Researching genes encoding these enzymes is crucial not only for TB but also for treating other severe diseases like cancer, cardiovascular disorders, and mental health conditions. The ability to predict drug efficacy and safety and adjust doses to minimize severe side effects could improve the quality of life for thousands.
Collaboration at the Intersection of Science and Medicine
The study was conducted by combining the expertise of three leading research institutions and specialists, including pulmonologists, chemists, pharmacists, and human genetics researchers. It began with the idea of collaboration to gather diverse data and determine whether human genetic variations influence the effect of anti-TB drugs. After obtaining the necessary approvals, patients were invited to participate, enabling researchers to study how their bodies responded to medications and whether this influenced treatment effectiveness. "We are deeply grateful to all the patients who agreed to participate in this study, as their involvement made this research possible," says Renāte.
Scientific Precision and Patient Well-being
"Collecting biological samples, conducting genetic analyses, measuring drug concentrations, and analyzing data were not easy. We wanted to explore broadly and deeply to gather as much useful information as possible," says Renāte. Blood samples were collected during the study to obtain genetic information and measure drug levels at specific time points. At the same time, the DNA of TB mycobacteria was analyzed to identify mutations that might make drugs ineffective. Researchers from Rīga Stradiņš University, the Latvian Biomedical Research and Study Centre, and the Latvian Institute of Organic Synthesis collaborated to link all the collected data, gaining essential insights to help patients recover faster.
New Tools and Methods for Drug and Metabolite Detection
During the project a new method was developed in collaboration with the Latvian Institute of Organic Synthesis to simultaneously detect four drugs and their six metabolites from a small blood sample. This method provides vital information about how quickly drugs are metabolized and helps evaluate patient responses to treatment. Additionally, a new analysis method was created to rapidly identify genetic changes along entire genes. Such methodological advancements are crucial for understanding drug efficacy at an individual level – whether drugs accumulate excessively, are metabolized too quickly, or are influenced by specific genetic variations.
Practical Applications and Public Awareness
Given the continued importance of TB, especially in Latvia, the project helped to improve public understanding of treatment challenges. Research and innovations are valuable contributions, but it is essential to emphasize that while TB treatment is effective, recognizing symptoms and seeking medical attention as early as possible is crucial. From a practical perspective, one of the key outcomes was proving the importance of therapeutic drug monitoring (i.e. drug concentration measurements). It was found that many patients’ drug levels in the blood were not optimal, highlighting the need for precise therapy monitoring tools.
The study also sparked discussions about patient adherence to therapy and the impact of smoking. For example, the results showed that smokers were more likely to have the infectious form of the disease and stayed in hospitals longer. However, fewer smokers failed to complete treatment. "This surprised us, but upon reflection, it makes sense. Smokers, by staying in hospitals longer, are indirectly reminded of the importance of completing therapy. In contrast, outpatient-treated patients are more likely to 'disappear' from medical supervision," explains Renāte.
A Future of Personalized Treatment
Personalized treatment is the future, and we cannot rely on the assumption that one drug will work for everyone. The effectiveness of TB treatment varies significantly based on genetic, biological, and environmental factors, underscoring the need for more precise approaches. The results of this study demonstrate that standard therapy methods may not achieve optimal outcomes for all patients. Therefore, continued research is essential to develop personalized treatment regimens based on scientific evidence and individual characteristics. This approach will not only improve treatment outcomes but also help more effectively control the spread of TB in Latvia and globally.
The project "Tuberculosis Treatment: Exploring Perspectives of Personalized Therapy" (lzp-2020/1-0050) is implemented under the Fundamental and Applied Research program, funded by the Latvian Council of Science
