The future of epigenetic drugs

In the light of increasing knowledge on the role epigenetic factors play in disease, it is now becoming apparent that epigenetics could be ideal therapeutic targets - particularly taking into consideration that many of these epigenetic factors are reversible. Epigenetic drugs are incredibly potent and can help reverse abnormal gene expression that can result in various diseases.

In recent years, research efforts in this area have grown substantially to uncover the biological and chemical mechanisms of epigenetic drugs and their targets.  At the same time, pharmaceutical companies are making major investments in this field. Transparency Market Research predicts that the Epigenetic drugs and Diagnostic Technologies market will be worth an estimated $5.7 billion by 2018.

The ‘Epigenetic Drugs‘ series recently published in Clinical Epigenetics delves deeper into this arena with reviews covering the current and upcoming areas of investigation and the challenges that are faced by researchers when developing these drugs.

While epigenetic drugs have primarily been studied for their use in treating cancer, the increasing funding efforts and interest have opened up avenues for researchers to pursue their use in Alzheimer’s, asthma and a myriad of other diseases. So what does the current landscape of epigenetic drugs look like?

Cancer

The main focus point of epi-drug research has been looking into their use in cancer treatment. There are two basic types of epigenetic drugs being tested for this purpose:

  1. Histone deacetylase (HDAC) inhibitors

Histone deacetylase (HDAC) inhibitors, act by counter-acting the effect that cancer causes on histones that can lead to reduced function of tumour suppressor genes. These drugs enable the chromatin structure to become more relaxed, allowing transcriptional activation of these genes.

There are currently three HDAC inhibitors that have been approved by the FDA and they are all being used in the treatment of rare T cell lymphomas.

  1. DNA-methytransferase (DNMT) inhibitors

DNA-methylation (DNMT), inhibitors operate by preventing the addition of methyl groups to genes in cancer cells. This is effective as DNA methylation results in gene silencing in genes that reduce the speed of cell division, resulting in uncontrolled proliferation.

Two drugs that inhibit DNA methylation, azacitidine and decitabine, have been approved by the FDA and are being utilised in the treatment of blood cancer.

There is now a greater understanding of how epigenetic factors come into play in the development of several chronic respiratory diseases including asthma and COPD.

Respiratory diseases

There is now a greater understanding of how epigenetic factors come into play in the development of several chronic respiratory diseases including asthma and COPD. Several of these factors are also reversible, so they can be ideal targets for therapeutic intervention.

An initiative has been started by MRC Technology and AstraZeneca to discover new epigenetic drug targets for respiratory diseases such as asthma and COPD.  Their aim is to work with academics researching epigenetic mechanisms in this area to collaborate on creating novel small molecule drugs that can target the epigenetic pathways for these diseases.

Alzheimer’s disease

There are currently a few epigenetic drugs in development that target Alzheimer’s disease. These drugs aim to alter gene expression and target genes that are linked to learning and memory. Things are looking hopeful as the first Alzheimer’s related epigenetic drug, ORY-2001, has been in development since 2010 and entered a Phase 1 clinical trial this April.

It still remains to be seen if researchers will be able to uncover the epigenetic mechanisms of disease, to allow more of these treatment options to become a reality.

The future

So what does the future of epigenetic drugs look like and what are the limiting factors holding back its advancement? The huge investments from the pharmaceutical industry will allow research to be expanded to develop therapeutic drugs in new fields. However, it still remains to be seen if researchers will be able to uncover the epigenetic mechanisms of disease, to allow more of these treatment options to become a reality.

Find out more in the Clinical Epigenetics ‘Epigenetic Drugs‘ series.

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