What Role Does Epigenetics Play in Drug Discovery?

By Sarah MooreReviewed by Ahmed Donia, Ph.D.

Epigenetics is being used to help identify DNA modifications that are implicated in diseases, therefore, suggesting new potential therapeutic targets to be explored in drug development.

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What is epigenetics?

The term epigenetics refers to the study of DNA modifications that do not change an individual’s genetic code, although they can influence gene expression. These modifications become apparent when certain genes are switched on and off.

In essence, an epigenetic change is when a chemical compound becomes attached to a single gene, having the impact of regulating its activity. The epigenome refers to all these epigenetic changes that have been made within the genome.

While these changes can remain in the cells as they divide, and in some cases can even be passed down to the offsprings, these modifications do not change the DNA sequence.

The epigenome can be impacted by a multitude of factors, such as an individual’s diet or exposure to pollutants.

Epigenetics has become a popular area of study in biology and healthcare because scientists have recognized its relationship with gene function, protein production, and essentially human health and disease.

Below, we discuss the role that is played by epigenetics in the field of drug discovery.

Using epigenetics in drug discovery

Epigenetics helped researchers to better understand how disease is established and inherited.

Also, it played an important role in unveiling how the disease develops and responds to therapeutic intervention.

It has been uncovered that many diseases have underlying epigenetic factors, which has opened up a whole new avenue for drug development by targeting these related mechanisms with newly established epigenetic drugs.

The first FDA-approved epigenetic drugs emerged less than two decades ago. Since that time, many more have been established, as research has continued to gain traction, reaching the point where epigenetics is now considered to lead the field in terms of novel drug discovery for several diseases, particularly for cancer.

The epigenetic mechanisms of chromatin remodeling, DNA methylation, and histone modification, which are crucial for gene and noncoding RNA expression, are the most focused areas of epigenetic study. These factors can help to determine a person’s epigenome.

Modern epigenetics relies on combining new and specialized methods to analyze genomic and epigenomic data. As a result of these practices, many studies have been able to reveal how epigenetics impacts disease.

These studies have also helped to identify new possible therapeutic targets. While cancer is the largest area where epigenetics is being used, studies into neurological disorders and autoimmune diseases are also using epigenetics to make great strides forward.

Below, we discuss how epigenetics has facilitated drug discovery for cancer, neurological diseases, and autoimmune diseases.

Epigenetics in cancer

The connection between epigenetic changes and cancer has been studied many times across several cancer types. BRG-/BRM-associated factor (BAF) complex, which is a highly polymorphic unit comprised of 15 subunits encoded by 29 genes, is the main area of study in cancer epigenetics. This is because they are mutated in approximately a fifth of all human cancer.

The current generally accepted opinion is that mutations in BAF complexes may likely be one of the leading underlying causes of all types of human cancer.

For this reason, they have become a major focus of drug discovery in cancer. In particular cancers, such as synovial sarcoma (SS), mutations in a specific unit of BAF complex have been identified.

In these tumors, no other mutations have been apparent, confirming that the BAF mutation is considered to be a major potential cause of cancer and a potential target for new therapeutic drugs.

Researchers agree that there is a need to clinically target BAF complexes, as currently there are no treatments in this area. In the coming years, we may begin to see these kinds of treatments emerge.

Epigenetics in neurological diseases

While several neurological diseases have been linked with epigenetic mutations, the relationship that has been uncovered between Alzheimer’s disease and these changes is perhaps the most significant one.

Lysine-specific demethylase 1 (LSD1) was the first-identified histone demethylase. Researchers recently showed the role of LSD1 in neurodegeneration and paralysis. In a recent experiment where LSD1 was eliminated from adult mice, researchers observed neurodegeneration and paralysis in these animals.

Researchers modeled that LSD1 played an essential role in Alzheimer’s disease (AD) and frontotemporal dementia, which further studies have confirmed.

It is believed that through further work and experimental studies, drug discovery through epigenetics will be advanced, potentially resulting in a new class of drug therapies for AD and other neurological disorders.

Epigenetics in autoimmune disease

Finally, a broad range of studies have been successful in identifying the epigenetic alterations that are related to numerous human autoimmune diseases, including autoimmune thyroid diseases (AITD), type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjogren’s syndrome (SS).

The work continues, with a focus on gaining insights into the pathogenesis of these diseases, which will hopefully lead to the identification of new drug targets.