Epigenetics and Novel Therapeutic Targets

Epigenetics is an emerging area of research, whose importance for generating novel approaches to therapeutics has become highly apparent since the sequencing of the human genome.  It concerns the analysis of cellular processes that are associated with and control the use of chromatin and the differential expression of genetic information encoded by DNA.  Epigenetic control explains why different cells in the body behave differently despite containing identical DNA information.  Errors in the epigenetic mechanisms result in aberrant cellular behaviour and can result in the development of disease including cancer, inflammatory diseases, cardiac disorders and degenerative conditions (including neurological diseases).  Epigenetics has led to a number of novel therapeutic approaches, mainly targeting various cancers.  It is now well documented that the majority of tumour cells display abnormal epigenetic patterns.

Multiple new classes of epigenetic enzyme targets are being discovered that are relevant for the development of small molecule drugs.  In addition, manipulation of epigenetic processes and pathways is important in regenerative medicine applications. 

It is now understood that there are many enzymes that have a direct or indirect impact on chromatin and gene expression.  Many of these enzymes are inappropriately expressed in disease conditions and constitute rational targets for combating disease.  The main initial focus has been on targeting histone deacetylases (HDACs).  However it has recently become clear that there is a wide range of novel enzyme families to target, many of which are highly tractable as drug targets.  

This is the focus for CellCentric – prioritizing and validating novel targets beyond HDACs and developing proprietary small molecule therapeutics.  

Understanding how epigenetic change occurs within cells, both in disease and in natural developmental biology processes (embryogenesis), is key to identifying novel targets and understanding their mechanism of action. CellCentric coordinates a number of direct research efforts in the area of cellular reprogramming; where cell fate is altered through epigenetic change.

CellCentric’s scientific founder, Prof Azim Surani is the pioneer who demonstrated that cell function can be made to change through modifying epigenetic processes, and that stem cell-like qualities can be induced through epigenetic imprint erasure. This type of knowledge has particular importance when considering novel targets to address proliferative and intractable tumour cell populations, sometimes known as cancer stem cells.