A surfing accident when she was 15 damaged Gabrielle Parent’s vertebrae and, though she recovered from the injury, she still suffers recurring lower back pain 20 years later.
Parent resists taking pain medication because, she says, opioids don’t help some people, cause harmful reactions in others and can be dangerously addictive.
“I’d rather not even risk it,” she said.
But what if she could reduce her risk? What if her physician could look at her genetic makeup and determine how her unique biology would likely respond to a specific pain medication?
This type of personally tailored treatment, called precision medicine, is one focus of a pain research registry at the University of North Texas Health Science Center called PRECISION TEXAS. UNTHSC researchers are exploring the impact that precision medicine could have on people suffering from everything from Alzheimer’s disease to diabetes.
PRECISION TEXAS focuses on people with low back pain, an affliction shared by 632 million worldwide. Parent, 35, of Bedford, has submitted saliva and blood for genomic and biomarker analysis and responds to quarterly questionnaires as part of her participation.
Every person has a series of genes for an enzyme that metabolizes codeine, a common ingredient in opioids that must be metabolized into its active form to have any effect. However, some people metabolize codeine too quickly and others hardly at all. As a result, they can suffer damaging side effects or no pain relief.
“The problem is, physicians do not commonly know these and other pain-related genotypes when they are prescribing the drugs to a patient,” said John Licciardone, DO, a professor at UNTHSC. “But if we knew the patient’s genetic makeup, we could use it to predict how that patient is likely to respond to the drug before we prescribe it.”
The result could be fewer patients suffering harmful side effects and better pain outcomes with fewer people at risk of addiction as physicians prescribe opioids more selectively.
TREAT PEOPLE, NOT DISEASES
What exactly is precision medicine?
The National Institutes of Health defines it as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person.”
Robert Barber, executive director of the UNTHSC Institute of Molecular Medicine, puts it more simply: “It means tailoring the treatment to the person, not the disease. That’s not the way medicine has historically been practiced.”
Health care providers often consider lifestyle and environment when making a diagnosis. When providers ask patients about their family medical history, they are referencing genetics.
But more recent advances in genomic medicine offer a more precise tailoring of medicine – a genome is an organism’s complete set of DNA.
Consider someone who suffers from depression, Barber said. There is an array of medications to treat the disorder and some work effectively in a higher percentage of people than others. However, some people won’t respond well to the most commonly effective drugs.
To determine which medication will benefit a patient, physicians generally prescribe the most common medication, monitor the patient’s response and, if necessary, work their way down the list to the less commonly effective medications.
“Each time you try a new a medication, there is a treatment period, a weaning period and a washout period to get it out of your system,” Barber said. “Meanwhile, there may be unpleasant side effects and the patient still has not gotten any relief.
“But with precision medicine, what if I could narrow down the 14 possible medications to the three medications that are most likely to help someone based on their genetics? That’s the kind of personalized treatment we are exploring.”
BIOLOGICAL MARKERS
Precision medicine could help researchers unlock the secrets of Alzheimer’s disease in post-menopausal women, who are two to three times more likely than men to get Alzheimer’s.
One possible treatment – hormone replacement therapy – carries some risks and may not be safe for all women.
“We are trying to identify a biological marker that predicts who among post-menopausal woman would respond favorably or unfavorably to hormone treatment,” said Meharvan “Sonny” Singh, a researcher and dean of the Graduate School of Biomedical Sciences at UNTHSC. “Rather than make a blanket statement that hormone therapy is bad, let’s see if it is a viable option for a certain subset of women.”
In most clinical trials, that subset of women is often ignored. For example, if a new therapy were to fail in 85 percent of study participants during a clinical trial, the science behind it is often scrapped.
But that also means the therapy was successful for 15 percent of the women in the trial. Using personalized medicine, researchers want to know if there was something common in the biology among the women who benefitted from the treatment.
“This focus on a subset of patients reflects a new way of thinking about clinical trials,” Singh said. “I would submit that the trial was not a failure for that 15 percent. The question is ‘What was it about the biology of those people that made it successful?’ ”
POTENTIAL AND CHALLENGES
At conferences, leaders in genome research sometimes hold up flash drives and announce that one day patients will carry a similar device containing all of their genetic information.
Perhaps, said Deanna Cross, a researcher at UNTHSC. Precision medicine has advanced beyond infancy – treatment is often already personalized for cancer patients, for example. But challenges remain.
The cost of genetic testing for one person can be as little as $100, but the cost of interpreting and storing that information can be exorbitant, Cross said. Physicians must be trained to understand the genetic information they are examining. Patient privacy must be protected.
Ethical questions must be answered as well, she said. What is the value in telling patients they are genetically predisposed to a disease if there is no therapy to help prevent it?
One way people can help personalize their own health care now is to create reliable family health histories, Cross said. She speaks to community groups about the importance of family health histories and shares online tools to create them.
“I call the family health history the $1 genome,” Cross said. “That information alone gives physicians a good idea of what diseases to look for and what strategies can help prevent them. The science is evolving, but you can start personalizing your health care right now.”
Alex Branch, a senior writer in the Office of Communication at UNT Health Science Center, spent 15 as a newspaper reporter, including 10 at the Fort Worth Star-Telegram, where he covered health care, hospitals, public health and nonprofits.
Jill Johnson spent 12 years as a photographer for the Fort Worth Star-Telegram before joining the Office of Communication in 1998.