Genetic Advances

Genetic maps point toward personalized medicine in near future

Gene testing may help manage Boomer health risks

By John "Boomer" Leighty

SAN DIEGO— Scripps Health is paving a path in personalized medicine with a three-pronged approach to genetic mapping for new treatments and cures for stubborn diseases, including afflictions of old age.

“Genomic medicine is no longer considered research,” says Eric Topol, MD, who leads three major Scripps initiatives on the cutting edge of genetics-driven medical practice. “We’re implementing a program that is the outgrowth of all the advances that represent state-of-the art care for patients today.”

Topol trailblazes the overall gene-related initiatives and in 2010 brought aboard prestigious gene sequencing expert Samuel Levy, PhD, as director of genomic sciences.

Levy heads a research team at the Scripps Translational Science Institute that interacts with comprehensive biological disciplines— so called “omic” sciences— to remove barriers for the adoption of DNA genomic analysis in clinical settings. He is also involved with an institute study on genetic underpinnings of healthy aging.

Some 1,400 genetic tests are available for use in clinical settings -- most looking at single genes used to diagnose rare hereditary disorders. However, a growing number of tests analyze multiple genes and utilize genomic technologies with a future potential to prevent widespread diseases such as cancer or diabetes.

Topol says the use of genetic testing to manage patients’ risk for various diseases, especially cancer, is becoming widely utilized by physician practices around the country.

Tests ID stent patient risks

In a practical application at Scripps, cardiac physicians have adopted a new genetic test to identify patients at high risk of severe complications from a common coronary procedure to unclog arteries pumping blood to the heart.

Cardiologists use a saliva test by Quest Diagnostics that reveals if a patient awaiting tiny metal tube implants called stents to enhance blood flow has hereditary mutations of the Cytochrome (CYP2C19) gene that causes rejection of anti-clotting medications, causing bleeding and more than doubling the risk of heart attack, stroke, or death.

Topol says about 30 percent of patients who undergo the procedure test positive for gene variants linked to an inability to metabolize the clot-busting drug Plavix (clopidrogel). This prompts physicians to use alternatives such as increased patient monitoring, a higher dosage of Plavix to overpower resistence, or the use of Effient® (prasugrel), a blood thinner.

For years researchers looked at various reasons for adverse reactions to anti-clotting drug therapy such as patient frailty, poor heart functions, or weakened artery walls, Topol says. “Well, it ends up not being that simple because the event is genetically determined. So, this marks a major step forward in individualized medicine by showing why people don’t respond the same way to a drug and looking at what we can do about it.”

There is an immediate economic impact since it costs $3 to $4 for a typical daily dosage of Plavix, a popular prescribed drug used by about one million heart patients in the U.S., Topol says.

“For patients who are not responsive to a drug they must take daily for the rest of their lives, this represents an immense amount of potential waste in the healthcare system.”

Scripps has the largest cardiovascular care network in California with 45,000 patients a year, and is designing a new heart institute projected to open in 2015, adds Topol.

Routine Genetic Tests

Some 1,400 patients a year now undergo elective stent procedures at Scripps Green Hospital adjacent to the clinic where genetic screening is being routinely offered in one of the first programs of its kind in cardiac care. For most insured patients, the procedure is partially reimbursed by health plans but may have high co-payments or deductibles and added expenses of a top-tier brand name drug.

“Everyone who enters the program will now have genotyping available,” Topal says. “The goal is far-reaching— never again to have patients with clotted stents.”

Patients should weigh privacy issues and potential benefits before making genetic testing decisions, he adds. “There are ways to go forward with a personalized medicine approach that looks at the unique DNA makeup of a patient.”

Genetics research has spawned innovative technologies and diagnostic tools that can measure more precisely the characteristics of a patient or disease for decision-making purposes. For example, finding the specific genetic qualities of a cancer tumor gives oncologists a powerful tool for targeting alternative treatments.

While there is a genetic component to risk, lifestyle choices and the environment make equal contributions. Researchers say an average patient’s whole genome sequence will reveal about 100 genetic risks.

Topol is also leading a 20-year initiative at the institute to determine whether patients actually try to improve their lifestyle and get regular checkups if they know they have a genetic predisposition for a disease. Researchers will assess the psychological impact of genomic testing on 10,000 adults taking part in the study.

The National Society of Genetic Counselors warns boomers and others that inexpensive direct-to-consumer genetic screening tests are being marketed that may be inappropriate or misinterpreted. In the absence of federal relations, consumers should get the advice of a genetic counselor or clinical geneticist before undergoing such testing.

Human Genome Project

The Human Genome Project sequencing of three billion base pairs of DNA wasn’t formally completed until 2003 when the cost of reading DNA finally approached $1 per unit, or $3 billion for a whole genome. Since then, it has guided researchers in investigations of human development and disease and a comparable genome sequence now costs less than $10,000. Some of the studies have yielded new tests and drug targets and insights into the basis of human disease and development. The research also reveals just how complicated human biology is, and how much remains to be understood.