- Category: Science
- Topic: Technology
Epigenetics is a field that plays a critical role in patient-based therapies such as epidrugs. It is well known that some diseases have reversible epigenetic features which can be addressed with pharmacological treatments known as "epidrugs". These drugs target specific enzymes, such as DNA N-Methyltransferase Inhibitor (DNMTi) and Histone Deacetylase (HDAC) inhibitors, with drugs such as Azacitidine, Decitabine, and Vorinostat being the most well-known.
Azacitidine and Decitabine target DNMTi whose role is the transfer of a methyl group to DNA. Inhibiting this enzyme through these drugs ensures that DNA methylation in chronic myelomonocytic leukemia and myelodysplastic syndrome is eliminated; although these drugs are not locus-specific, they have the potential to be used in many other diseases and gene locations. Vorinostat, on the other hand, targets the HDAC enzyme, which regulates the chromatin structure and transcription. While these single-agent epigenetic drug therapies are not very efficient due to the damage on intracellular pathways, researchers have proposed the idea of combinatorial epidrug therapy where DNMTi and HDACi are combined for more effective treatment.
Epigenetic biomarkers are another crucial aspect of epigenetics since they show whether the pharmacological therapy is working or not. For example, methylation of the promoter region of MGMT is associated with temozolomide, an alkylating neoplastic agent. This observation indicates that the decrease in methylation levels on the MGMT gene leads to the expression of O6 alkylguanine DNA alkyl transferase, which repairs DNA damage. Hyper-methylation, on the other hand, causes gene silencing, making the disease more sensitive to drug treatment. Similar biometric results are also observed in GSTP1 and BRCA1 genes.
Epigenetics is now being used for personalized medicine, especially for the modification of genes responsible for drug absorption, distribution, metabolism and excretion (ADME). These macromolecules encode proteins, enzymes, and transporters, which play vital roles in the absorption, distribution, metabolism, and excretion of xenobiotics. Genetic differences in these ADME genes help predict various pharmacokinetics, but the additional contribution of epigenetics plays a significant role in the differentiation of individual phenotypical variations. The epigenetic state of ADME genes is vital in disease phenotypes; for instance, hypomethylation of the CYP2E1 gene plays a role in Parkinson's disease, while CYP1B1 and CYP1A1 contribute to prostate cancer.
In conclusion, epigenetics is becoming increasingly essential in personalized medicine. It promises to improve treatments for diseases like cancer, Parkinson's, and schizophrenia. Therapies are now based on epigenetic findings such as DNA methylation and histone modification, targeting enzymes that regulate epigenetic activity. Epigenetics can also be used as a biomarker to identify unknown aspects of complex diseases.