Tailoring our drugs

Tailoring our drugs

Touro College of Pharmacy’s Zvi Loewy talks about pharmacogenetics

Dr. Zvi Loewy
Dr. Zvi Loewy

We know that physically all of us human beings are similar; our hearts pump blood out to our extremities, our lungs help the rest of our bodies get the oxygen we need, our brains regulate the whole thing.

But each one of us is different, too; the case can be made that on the finest level, each one of us is unique. A perfect snowflake.

Given that, why should doctors assume that our bodies will respond in exactly the same way to any medication?

They don’t assume that, as it turns out; now, they’re at work figuring out how to understand the differences and prescribe to them.

Dr. Zvi Loewy of Fair Lawn led a team of researchers at the Touro College of Pharmacy as it investigated how to tailor pain medication to patients based on their genetic profiles. The study, published recently in the Journal of Personalized Medicine, looked at 107 patients who suffered from chronic pain. The developing field of pharmacogenetics determined that — to be entirely untechnical — some of them were being overdosed, some underdosed, some inappropriately dosed. The results of the study were that many of them were able to have their pain ameliorated.

“The study focused on the newly emerging field of pharmacogenetics,” Dr. Loewy said. “We know that if you come down with an infection, you go to your physician, and your physician puts you on an antibiotic, and it might work or it might not work, and the physician might have to change the dose.

“That’s how this works in general. We are all individuals; just as we have preferences in terms of what we eat and what lifestyle we chose,” so too the body has its own preferences. “This is the era of personalization,” he continued. “You have a personalized trainer. You go to a pizza shop and get a personal pizza.” You’ll do better at reaching your goals with a trainer who focuses on you, and certainly you’ll like your pizza better if you to put pineapple on it, even if your partner thinks that’s grotesque.

“Medication is going in that direction too,” Dr Loewy said. “It’s not one drug or one dose that fits all.

“What we set out to do in this paper is to address the problem of people who suffer from chronic pain — and we really feel for them — and go to their internist, who throws up his or her hands and says, ‘This is as much as I can do for you.’”

Pharmacogenetics can help doctors figure out what more they can do.

“We all know people who can eat as much as they want and never gain a pound,” Dr. Loewy said. “And we know people who just look at food and gain weight. In terms of how our bodies metabolize drugs, it’s the same thing. It’s correlated with our genetic makeup; we are all individuals. Our genomes are very similar, but there is variability, and it is in that variability in our genome that is responsible for differential metabolism when it comes to drugs.

“It means that some people won’t metabolize a specific drug,” he continued. It won’t work for them at all. “Other people might metabolize it too rapidly, so it will go out of the body right away.”

Dr. Loewy and students walk together at the Touro College of Pharmacy in Manhattan.

Normally, “when a physician initially puts a patient on pain medication, he assesses how well the medication is working based on the conventional ‘How are you feeling? How is your pain?’ based on a scale of 0 to 10. We’ve all seen those questions.” We’ve all seen the smiley to frowny faces that accompany that scale, too.

But the problem with that scale is that it’s subjective. For the study, Dr. Loewy and his partners worked with cheek swabs. Those cells, scraped from the inside of a patient’s cheek, were sent to a clinical reference lab, “just like you would send off a couple of tubes of blood from an annual physical.

“The lab performs the genetic testing for specific genes that are known to be involved in drug metabolization,” Dr. Loewy said.

“When the physician gets the results back, the results tell if this patient is a normal, a poor, or an ultra-rapid metabolizer for this class of drugs. Depending on the results, the physician will reassess the pharmacotherapy for each patient. It will be personalized based on the test results.

“When the results of this study came back, the physician changed either the dose or the method of delivery — sometimes it could be delivered as a patch, as opposed to an oral delivery system. We found that those patients who suffered from very intense pain were the ones who responded best as a result of the testing. So when the physician changed the medication route — either the drug dose or the method of delivery — they all responded, and said ‘we are feeling a lot better. Our pain is being alleviated.’

“That’s a tremendous breakthrough in terms of treating patients specifically for common pain.”

Understanding how a patient metabolizes a drug can help forestall such tragedies as one Dr. Loewy quoted from a New England Journal of Medicine paper published a few years ago. A toddler who frequently got sore throats had gotten a tonsillectomy. “Before the child was released, the hospital gave the parents a prescription for codeine to help with the pain. The parents gave the child the codeine, and the child went into respiratory distress. Within 36 hours of being released from the hospital, the child passed away.

“That is because the child was an ultra-fast metabolizer for codeine, so his body made it into morphine, which killed him.”

Pharmacogenetics are being used in ways outside the scope of his recent study, Dr. Loewy said, including for cardiovascular problems and in psychiatry and oncology. It also can be used to help treat covid-19, he added. That’s because some existing drugs may help some minority of covid patients; “if we can identify 30 or 40 percent of the population who will benefit from it, that would be a huge win.

“That’s where the pharmaceutical industry is going,” he said. “Historically, it’s been all about developing a blockbuster drug because one drug fits all. Now we know that’s not necessarily true. If you can come up with three or four drugs, that’s where we want to go. And if we can repurpose drugs by identifying the population, we will have made tremendous inroads in their therapy.”

The bigger the database that pharmacogenetics can develop, the more precisely patients can be treated. “For each person, you have to get a sample,” Dr. Loewy said. “Once you do the baseline genetic analysis for an individual, then you basically go into a database that shows which drug will work with the specific individual’s genetic profile.”

It also can be helpful in helping patients whose pain-related opioid use might spiral into addiction. “This could be a way of controlling the addiction,” Dr. Loewy said. “That would be huge.

“The key message is that with this new technology, treatment will be tailor-made. Your physician will order lab tests from a swab of your cheek. Whatever drug you are going to receive will be specific to you. Hopefully, people will respond much better to them.”

In order to make this work, “everyone should get tested,” Dr. Loewy said. Don’t assume that if your parents or siblings are tested, you know what your genetic make-up is. “We are all different,” he said. “With the exception, probably, of identical twins.”

read more: