Epigenetic therapy

Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms, and epigenetic therapy offers a potential way to influence those pathways directly.

Many diseases are known to have a genetic component, but the epigenetic mechanisms underlying many conditions are still being discovered. A significant number of diseases are known to change the expression of genes within the body, and epigenetic involvement is a plausible hypothesis for how they do this. These changes can be the cause of symptoms to the disease. Several diseases, especially cancer, have been suspected of selectively turning genes on or off, thereby resulting in a capability for the tumorous tissues to escape the host’s immune reaction.

Known epigenetic mechanisms typically cluster into three categories. The first is DNA methylation, where a cytosine residue that is followed by a guanine residue (CpG) is methylated. In general, DNA methylation attracts proteins which fold that section of the chromatin and repress the related genes. The second category is histone modifications. Histones are proteins which are involved in the folding and compaction of the chromatin. There are several different types of histones, and they can be chemically modified in a number of ways. Acetylation of histone tails typically leads to weaker interactions between the histones and the DNA, which is associated with gene expression. Histones can be modified in many positions, with many different types of chemical modifications, but the precise details of the histone code are currently unknown. The final category of epigenetic mechanism is regulatory RNA. MicroRNAs are small, noncoding sequences that are involved in gene expression. Thousands of miRNAs are known, and the extent of their involvement in epigenetic regulation is an area of ongoing research.

A common symptom of diabetes is the degradation of blood vessels in various tissues throughout the body. Retinopathy refers specifically to the damage resulting from this process in the eyes. Diabetic retinopathy is the leading cause of blindness in the United States. Diabetic retinopathy is known to be associated with a number of epigenetic markers, including methylation of the Sod2 and MMP-9 genes, an increase in transcription of LSD1, a H3K4 and H3K9 demethylase, and various DNA Methyl-Transferases (DNMTs), and increased presence of miRNAs for transcription factors and VEGF. It is believed that much of the retinal vascular degeneration characteristic of diabetic retinopathy is due to impaired mitochondrial activity in the retina. Sod2 codes for a superoxide dismutase enzyme, which scavenges free radicals and prevents oxidative damage to cells. LSD1 may play a major role in diabetic retinopathy through the downregulation of Sod2 in retinal vascular tissue, leading to oxidative damage in those cells. MMP-9 is believed to be involved in cellular apoptosis, and is similarly downregulated, which may help to propagate the effects of diabetic retinopathy.

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