Epigenetics is a field of science that has attracted significant attention of late, and although the term has been around for some time it has really only since about the late 1980s been used in its current sense in biology and drug discovery. In essence, epigenetics refers to covalent changes (frequently methylation, hydroxymethylation or acetylation) of either DNA or histone proteins. Such changes do not affect the sequence of translated proteins, but they do alter the way such proteins may be expressed. Such alterations are potentially heritable, although this is not without its detractors, is becoming generally accepted. Such mechanisms have attracted significant attention in the Pharmaceutical industry, principally as possible therapies for cancer, where over-expression of certain proteins may have a significant part to play in the pathogenesis of the disease. I’ve chosen to concentrate on applications other than cancer, as that avenue has been well-trodden by others.
The free downloads available in this newsletter highlight some of the most recent developments in epigenetics, highlighting research into the effect of epigenetics in chronic diseases, in eye disease and heart development and disease.
The first article, by Shannalee R. Martinez, Maresha S. Gay and Lubo Zhang of The Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA entitled: “Epigenetic mechanisms in heart development and disease” describes how developmental issues in utero can be responsible for chronic disease in the adult and how evidence for an epigenetic driver for these processes is gaining acceptance. The article reviews the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease and how this may represent a target for pharmacologic intervention in such disorders.
The second article, from Faith A.A. Kwa and Thilini R. Thrimawithana of RMIT University, Bundoora, VIC 3083, Australia entitled: “Epigenetic modifications as potential therapeutic targets in age-related macular degeneration and diabetic retinopathy” outlines the recent observations that epigenetic changes have been observed (and may drive) pathology in a number of posterior compartment eye diseases. In particular, the review looks at the epigenetic component of age-related macular degeneration (AMD) and diabetic retinopathy. They propose that molecules that may modify the epigenetic component may be able to assist either as monotherapy or as agents that may improve the efficacy of existing agents.
Finally, is the review from Qinqin Gao, Jiaqi Tang, Jie Chen, Lin Jiang, Xiaolin Zhu and Zhice Xu of The Institute for Fetology, The First Hospital of Soochow University, Suzhou 215006, China and The Center for Prenatal Biology, Loma Linda University, CA 92350, USA, entitled, “Epigenetic code and potential epigenetic-based therapies against chronic diseases in developmental origins”. The authors review the growing evidence supporting the involvement in epigenetics with respect to prenatal stress and the developmental programming of chronic disease in the adult. They comment that since epigenetic changes are potentially modifiable, possibly even reversible, pharmacologically, then it follows that drugs designed to affect epigenetic change may be useful candidates for drugs capable of treating chronic disorders, with a mechanism that is significantly different from current approaches.
Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents. Earlier this month, Steve and his band were unsuccessful in their attempt to become Brass Band Champions in the finals at Cheltenham. Despite a creditable performance of The Alchymist’s Journal, the band was not highly ranked by the judges. Whether this performance will be enough to raise Steve into the top 200 of 2nd tenor horn players remains to be seen.