Team:Patras/Description
Description
- Project Hippocrates
Hippocrates is an innovative diagnostic tool that aims at the implementation of Pharmacogenomics into clinical practice. Personalized medicine is achieved by adjusting the proper administered dosage of drugs, reducing the adverse drug reactions. We present the BentoLab- AI system, a portable molecular laboratory in the size of a hand-luggage combined with Artificial intelligence, to directly provide the physician with the recommended adjustment of the statin dosage according to the patient's genotype. Taking into consideration that the physicians are not adequately qualified to perform such a genomic analysis, we provide a step-by-step guide with the details, advice, photos, and videos through a web application that needs to be followed to perform the experiment successfully.
- Why Hippocrates?
Hippocrates of Kos was a Greek physician of the Age of Periklis (Classical Greece), who is considered one of the most outstanding medical history figures. He is also referred to as the “Father of Western Medicine” to recognize his lasting contributions to the field as the Hippocratic School of Medicine founder.
He established medicine as a profession distinct from other fields with which it had traditionally been associated, like theurgy and philosophy.
As Hippocrates said, “It is more important to know what kind of person suffers from a certain disease than knowing from which disease somebody suffers.”
Our project is called Hippocrates due to his contribution to Pharmacogenomics. Although personalized medicine wasn’t ubiquitous in Hippocrates’ era, he accomplished to apply it in his occupation. Thus, he blazed the trail for future scientists to search throughput the field of Pharmacogenomics and institute it into clinical practice.
- What is Pharmacogenomics?
Pharmacogenomics describes the differential effects in patients who receive the same dosage of a drug due to differences in their genome profile, which can subsequently contribute to treatment individualization.
Pythagoras around 510 BC first recognized pharmacogenomics. He was the one associating the dangers of fava bean ingestion with hemolytic anemia and oxidative stress. This identification was later validated and attributed to the detection of G6PD deficiency in the 1950s and called “favism.”
This relatively new field combines pharmacology and genomics to develop effective, safe medications and doses tailored to a person’s genetic profile.
Pharmacogenomics aims to optimize drug therapy to ensure maximum efficiency with minimum adverse effects concerning the patient’s genotype. Through the utilization of pharmacogenomics, it is hoped that pharmaceutical drug treatments can deviate from what is said as the “one-dose-fits-all” approach. Pharmacogenomics also attempts to eliminate the trial-and-error method of prescribing, allowing physicians to consider their patient’s genes, the functionality of these genes, and how this may affect the efficacy of the patient’s current or future treatments.
- Hypercholesterolemia
Hypercholesterolemia, a form of hyperlipidemia, is the presence of high cholesterol in the blood. Raised cholesterol levels is a high-risk factor for causing heart disease and stroke. Specifically, a third of ischaemic heart disease is attributable to high cholesterol, according to WHO. It is also estimated that increased cholesterol causes 2,6 million deaths per year (4.5 percent of total deaths).
In Greece, 46 percent of men and 40% of women have general serum cholesterol levels >200mg/dl. Of them, 40% of men and 30% of women were ignorant of their condition, while 31% of men and 20% of women receive pharmaceutical treatment (especially statins).
- Statins – SLCO1B1 – OATP1B1
Europe has the highest percentage of people with raised cholesterol (54% of both sexes), followed by America with 48% for both sexes.
Statins are prescribed by physicians to control cholesterol but in random doses, according to previous cases’ experience.
According to PharmGKB, the polymorphism we are studying has a directive to avoid simvastatin in patients who are homozygous for the polymorphism rs4149056 of this gene. It is also reported that atorvastatin’s and fluvastatin’s metabolism is affected (albeit to a lesser degree) by the same polymorphism. The study aims to personalize statins’ dosage to avoid the severe side effects of statins such as rhabdomyolysis and hepatopathies.
Statin-associated muscle symptoms (SAMS) are frequently a cause of statin nonadherence and drug discontinuation. The rs4149056 is associated with reduced activity of the hepatic OATP1B1 (organic anion-transporting polypeptide) transporter and increased plasma concentrations of simvastatin.
Organic anion-transporting polypeptides (OATPs) mediate the uptake of a vast amount of compounds into cells. Substrates for the OATP family members include hormones and steroid conjugates and drugs like statins, cardiac glycosides, and anticancer agents like methotrexate.
SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. Recent American Heart Association / American College of Cardiology recommendations on cholesterol, increase the population qualified to receive statins even if they do not have clinically overt cardiovascular disease.
This guideline raises the number of patients potentially at risk for SAMS. Studies have shown the association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. A composite adverse event (CAE) is defined as discontinuation for any side effect, myalgia, or Creatine Kinase (CK) 3 times fold upper limit of normal during follow-up. Although the precise mechanisms for statin-induced side effects are unknown, they likely are caused by a combination of patient and statin characteristics. Several patient-specific risk factors, such as older age, reduced body mass, hypothyroidism, and female sex, were established..
Personalization in the administration of statins can prevent some of its side effects and optimize their action. The challenge here is to analyze the genome for the SNP tested quickly and determine the dosage of statins based on PharmaGKB guidelines.
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16 students from Patras blending Pharmacogenomics with Artificial Intelligence to redefine medicine
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