Metabolomics and Personalized Medicine : Benefits, Part 2

by Food and Drug Administration (FDA)

(Page 3 of 3)

At Duke University Medical Center, researchers are looking for metabolic biomarkers for breast cancer, says Newgard. By identifying metabolic profiles of malignant vs. nonaggressive breast tumors, they are hoping to be able to detect the presence of malignant tumors at an early stage when they are most treatable.

"The application of metabolomics can run the gamut of every sort of health care situation that you can imagine," says Newgard, including weight loss. Newgard and his research team are charting the metabolic changes that occur in people who lose weight using eight different weight-loss methods, ranging from the Atkins diet, to weight-loss drugs, to stomach-stapling surgery.

How will this work help people lose weight? "In the most optimistic sense," says Newgard, "you can imagine that in the future when an obese person wants to lose weight, a first step in the process would be to get that individual's baseline metabolic profile." Then based on a person's metabolic condition and information gained from studying weight-loss interventions, scientists might be able to predict and recommend the particular weight-loss method most likely to work for the person. "That is the ultimate possibility," says Newgard.

"Another strength of metabolomics is to follow an individual over time," says Dragan. Research is moving toward using metabolomics to monitor disease, she says, by looking at different stages of the same disease across time in an individual or within a group of people, such as in clinical trials.

"You can monitor healthy people, too," says Dragan, to catch diseases early. "If somebody has a disease, the metabolite patterns look different than if they don't have that disease."

What Is the FDA's Role?

Metabolomics and other -omic technologies are likely to have a dramatic impact on the FDA's regulatory mission over the coming decade, says Dragan. "We know that in the future companies will be submitting data for new products based on metabolomic studies." The agency must seek new ways to evaluate the performance and safety of drugs and diagnostic tests that employ metabolomic technologies. And FDA scientists must gain the knowledge to be able to specify standards and procedures for the performance of metabolomic studies and for the submission of data.

In anticipation of this regulatory responsibility, FDA scientists at the NCTR are conducting basic research to better understand the technologies and science of metabolomics and their use in product development and evaluation. They also are collaborating with medical institutions and drug companies that are doing metabolomic research on nonproprietary agents.

"Through this collaboration, the FDA can leverage its limited research dollars to be able to extend its expertise," says Dragan. "Both sides are learning how to apply the technology. It's a way that we can work together in order to bring the best science to the problem at hand." What Are the Challenges?

Although the potential benefits of metabolomics are great, so are the challenges to using the science to advance public health. One of these challenges is determining the significance of metabolomic changes. "Finding changes in metabolite profiles is not a problem," says Beger. "It's figuring out what these changes mean."

Researchers must distinguish between changes caused by a drug or by some other influence, such as diet. "Diet plays a large role in metabolizing drugs," says Beger. "Humans can eat thousands of different small molecules at any one sitting," says Beger, "which can affect the way a drug is metabolized."

Robertson sees metabolomics as "a molecular way to do what physicians have done for thousands of years," which is to diagnose patients based on a combination of symptoms that indicate a disease. If a patient has a rash and fever, for example, a rash by itself may not be enough of a clue, says Robertson, "but combine that with a fever and other symptoms, then it's an indicator."

"We do the same thing at a molecular level. The challenge is to identify molecules or patterns of molecules, out of tens of thousands of metabolites, that are specific enough to use as biological markers."

The complexity of the technology required to do metabolomic studies is another challenge, says Newgard. "I think there is a perception by some that you buy one of these sophisticated mass spectrometer instruments and you start squirting stuff into it and it gives you the data — and it's not like that at all. It's actually fairly hard analytical chemistry, and it takes rigor and dedication."

"Perhaps the greatest challenge is that our ability to generate masses of data far outstrips our capacity to understand it," says Robertson. Every sample of fluid analyzed requires measuring hundreds of substances, and all of these measurements produce data.

The data will also present regulatory challenges for the FDA. As drug and device makers incorporate metabolomics into their research, development, and testing of products, the agency must be prepared to evaluate the large quantities of data that these companies will submit to support clinical trials and product approvals.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.