From Research to Therapy
The CSC and Imperial College London hosted this year’s International ADMA Symposium, bringing together sixty leading researchers from around the world investigating the biology, physiology and pathophysiology of ADMA. With ADMA research approaching the point where basic scientific discoveries can be translated into improved healthcare, the two-day conference provided an ideal forum to discuss future directions critical to its continued progress.
ADMA (asymmetric dimethylarginine) is an amino acid that is found naturally in blood and is produced by the methylation and subsequent break down of proteins. It is known to interfere with the generation of the cell signalling molecule nitric oxide – a key player in maintaining our cardiovascular health. Consequently abnormally high levels of ADMA are associated with cardiovascular disease, as well as diabetes and kidney dysfunction, making the study of this small chemical of significant therapeutic importance.
Walter Fast, of the University of Texas, speaking on the process of methylation that results in the production of ADMA said, “The methyl mark, even though small, is an important contributor to the larger picture of health and disease”.
This year’s symposium covered the breadth of ADMA research, from its biochemistry, physiology and genetics to its disease relevance and how we can intervene to modulate ADMA levels in humans. Opening the symposium with the biochemistry of ADMA immediately brought to light controversies in the field that stimulated discussion throughout the course of the conference. Of particular note was the on-going debate on the relative roles of the enzymes DDAH1 and DDAH2 in regulating ADMA levels.
The series of talks progressed from research at the level of isolated proteins and cultured cells to the significant contributions of animal models and finally ADMA in a clinical setting. The latest findings on the role ADMA has to play in a host of human diseases were presented, covering cardiomyopathy, obesity, diabetes, heart failure and chronic kidney disease. The wealth of ADMA research discussed across the two days of talks, poster sessions and deliberations was set into the wider context of disease therapy by the key note speaker Patrick Vallance, President of pharmaceuticals research and development at GlaxoSmithKline.
Vallance, working together with Professor Sir Salvador Moncada at St George’s Medical School, was the first to identify the effect of dimethylarginines on nitric oxide synthesis. Now focused on discovering new drugs for therapy, Vallance asserted, “We are entering a new era where the past two decades of science are about to translate into medicines and the effect on human health will be profound”.
Researchers in ADMA, including CSC’s own James Leiper (Nitric Oxide Signalling Group) who organised this year’s symposium, continue to investigate how this small but significant chemical affects our health, with the ultimate goal of translating these findings into medical interventions in the coming years.