Roger Foo: Genetic research holds out new hope in battle against heart disease
SINGAPORE
Many of us remember what we were doing on the day of a significant global event. The day that airliners were flown into the World Trade Center and the Pentagon. The day that the Berlin Wall came down. The day that a tsunami hit the shores of Indonesia.
As a physician, I remember one day during my ward rounds in 2000 when then-British Prime Minister Tony Blair and then U.S. President Bill Clinton announced that the full human genome was finally sequenced. While it was inspiring to hear that the “blueprint” of humans was now known, I still had sick patients on my list yet to be seen and discharged. For them, the relevance of the discovery could not have felt more remote.
Not every advance is momentous. Most ground-breaking changes cannot be pinpointed to a single press conference. They are instead the result of many smaller, incremental advances, as we cardiologists would be soon be reminded.
Around the time we first understood the human-genome sequence, we discovered that humans have virtually the same number of coding genes (roughly 20,000) as a worm or fish.
What makes us different are the 3 billion remaining base pairs of the non-coding genome. In these, we find what are called gene regulatory elements. They are more easily visualized as “switches” that control when and how much our genes are expressed.
The blueprint of the human genome can be thought of as a songbook. Different musical notes are sung by different cells, often in unison. And so, we have lung cells performing differently from heart or liver cells even though they all have the same blueprint. The circuitry involved is intricate.
Despite this complexity, now is a fantastic time to be working in genomic research. Technological advances reveal how different sections of the genome and its switches underpin cellular functions throughout the body. With technology, doctors can sequence our patients’ genomes at accessible cost, control their gene expression and even edit their blueprint. This lets us target the root cause of diseases.
Indeed, such technology has already informed life-saving new therapies for cancer. When cardiologists watched Mr Blair’s and Mr. Clinton’s 2000 announcement, it kindled hopes for new cures and therapies. Now, we’re finally moving closer to such solutions for complex and multifactorial heart diseases.
For example, mapping out the genes that cause high cholesterol has had a huge impact. We now think that it may be possible to safely edit such genes in adult genomes, giving people a reduced risk or even lifelong protection against heart disease. In the meantime, suppressing gene expression related to heart disease using twice-yearly injections of gene-targeting medicines will be far more effective than the daily oral doses of statins that patients currently take.
A new generation of medicines is emerging as a result of our ever-deepening understanding of the genomic map. Targeting genomic switches in order to reprogram gene expression would reverse the course of disease rather than simply slow its progression. The latter is what nearly all medicines today do.
The future of cardiology glows with excitement as we pursue a solution to the scourge of heart disease, which blights the lives of many – particularly those at elevated risk, such as the elderly and sufferers of metabolic diseases and diabetes. These risk factors are at an all-time global high. For cardiology, the next generation of ground-breaking medicines is firmly on its way and could not be welcomed sooner.
Roger Foo , M.D., is Sheikh Zayed bin Sultan Al Nahyan Professor in Medicine at the National University of Singapore.
Human genes by function of the transcribed proteins, as number of encoding genes and percentage of all genes