The 99% Solution

Approximately 99% of the population take medicines without a problem. But some people experience dangerous reactions, which can force the FDA to pull drugs from the shelf, denying patients needed help and costing drug companies billions. Researchers with The Hamner–UNC Institute for Drug Safety Science are trying to understand why.

RESEARCH TRIANGLE PARK - Headaches. Backaches. Sore muscles. High blood pressure.

Whatever the issue, most of us simply take medicines to address our medical condition and forget about it. We’re not really worried about safety issues, trusting that by the time a medication is available for sale on store shelves, it has been thoroughly tested and determined to be safe.

And most of the time, medicines work the way they are supposed to work. In fact, for roughly 99% of patients, the medicine does what is expected without any problems. The odds of a patient experiencing a rare drug reaction are remote; about one in ten thousand cases. But if there is a problem, the ramifications can have far-reaching affects, beyond the individual patient who is having the reaction.

Bad drug reactions can delay the approval of a new drug. That not only lengthens the amount of time it takes to get a drug to patients, but it’s also expensive when you consider it takes almost 10 years and costs more than two billion dollars to bring a new drug from discovery in the lab to when it is sold on store shelves. Bad drug reactions can also halt the sale of a drug that is already on the market.

The trouble is, since medicines work well on the majority of people most of the time, what caused the reaction is often a mystery. To find the answer, pharmaceutical companies call on the scientists at The Hamner–UNC Institute for Drug Safety Science. It’s one of only two such research facilities in the world.

“We have the ability to explain why and that’s helpful when it comes to informing the next drug to be made to make sure it is even safer,” says Dr. Paul Watkins, Director of the Hamner-UNC Institute for Drug Safety Sciences. “But more recently, we’ve been able to go farther than that, and not only explain why, but develop a strategy to control or manage that risk. That usually means personalized medicine. So we believe we can use the tools we created over the past six years to solve the problems by identifying the patients who are going to have these severe reactions to the drugs.”

The Hamner Institutes, with its history of studying chemical safety, partnered with University of North Carolina at Chapel Hill Schools of Medicine and Pharmacy to better understand what are called rare drug reactions. Dr. Watkins says the experience and expertise the two institutions bring to the drug safety issue is unparalleled.

“We understand the biology of the disease, we understand what targets we want the drug to interact with, and we understand that at times hitting one target is not enough because of the redundancy of mechanisms," adds Dr. Watkins. “So we know there are times you want to hit more than one target to help a medical issue. And while we understand all that, we also understand that some patients react differently.”

Researchers bring an array of technology to try and understand the “why” of a drug reaction. Joe Trask uses cellular imaging to study a cell’s health. Individual cells are a lot like the people they make up. You can learn a lot from a snapshot.

“We are interested in determining whether the cell is undergoing some programmed cell death,” says Joe Trask, Cellular Imaging Core Chief, at the Hamner Institutes. Trask is showing me cell images on the computer screen. “With these images, we can see whether the cell membrane has been compromised. We also stain the cell with different fluorescent probes, and that helps us find the nucleus so we can measure it, and actually determine where it is in the image so we can make measurements of it.”

Down the hall, Dr. Merrie Mosedale works to see if part of the answer to a drug’s toxicity can be found in a patient’s genes.

“If we can identify the particular gene variants that are causing the drugs to be harmful for that small number of people, we can screen people and identify people who are going to have a positive response with no problem, and those who are going to have a bad response,” says Dr. Mosedale, a research investigator with The Hamner Institutes. “That way we can keep those people from taking the drug and let everyone else take the drug safely. It may also be possible down the road for a pharmaceutical company to redesign the drug in such a way that it would protect those who had a negative reaction but still provide the medicinal benefits of the drug.”

Because it has been so successful, the drug safety partnership with UNC has been renewed. Dr. Watkins credits that renewal with the Institute’s unique mission: focusing science and the scientific techniques available not to see who will have the greatest benefit but to identify the rare patient who will be harmed.

“What I think is the most exciting thing is that with this technology, we can get drugs to the patients quicker and at much lower cost, which will translate into cheaper medications,” adds Dr. Watkins.

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