Columbus Monthly Special Section: Health Matters

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TARGETED TREATMENTS A look at the latest advancements in personalized medicine being utilized in Central Ohio.

By Peter Tonguette

You might call it instant-gratification medicine.

When Dr. Angela M. Hardwick, a neurologist at OhioHealth, performs an operation to place a deep-brain stimulation (DBS) implant to treat patients suffering from Parkinson’s disease and other movement disorders, like essential tremor, the results can be detected right away. Sometimes, Hardwick will ask a patient—who, until the procedure, had been experiencing unsteadiness

in their hands—to jot down a note on a piece of paper.

“When it gets to the right spot, and we program it just right, in the operating room I have them write a note to their family,” says Hardwick, who performs the operation while the patient is awake, numbed by local anesthetic. “It’s an amazing feeling for them. They haven’t seen their handwriting in years—it’s steady, it’s clear. [Patients] most typically write, ‘I love you,’ to their wife.”

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If you find yourself tearing up at such a thought, you’re not alone. “That actually is why I decided to go into movement disorders,” Hardwick says. “I saw this in training and I said, ‘This is where I need to be.’ ” The implant is one of many high-tech solutions trending among Central Ohio physicians and their teams. While much of the current news coverage is centered on COVID-19, local health care providers continue to offer innovative, impactful treatments for a variety of conditions.

DBS involves the placement of electrodes, or lead, in particular portions of the brain; a device that regulates the electrodes’ stimulation, similar to a pacemaker, is implanted in the chest. The physician switches the device on, and makes any adjustments, in a follow-up visit.

The procedure can be considered after oral medication fails to control a patient’s symptoms, but, since its introduction nearly 20 years ago, it has increased in use.

“Initially, it was in research trials, and there weren’t a lot of people who trained to be able to do this,” Hardwick says. “Now you can get it in most states. … I find that the more people are kind of getting familiar with it, the more that people are actually opting for it.” Plus, as the nation’s population ages, there is a greater pool of individuals who

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receive diagnoses of Parkinson’s and thus might benefit from the procedure.

Exactly how DBS mitigates symptoms remains a subject of controversy and uncertainty among physicians, but one thing is clear: Symptoms should be expected to improve by at least 70 percent, and sometimes more, according to Hardwick. “There are certain cascades in the brain that you need to either activate or turn off, and so we think that the DBS is able to assist in that process of causing the brain to say ‘Go, go, go,’ or ‘stop, stop,’ ” Hardwick says. “We don’t exactly know completely why, but it works.”

In fact, the brain is the site of some of the most exciting treatments for other conditions, including Huntington’s disease. An inherited disorder in which huntingtin proteins cause brain-cell breakdown that leads to impairment in movement or cognition, Huntington’s has traditionally been tough to treat.

A recently launched five-year, double-blind, randomized clinical trial at the Ohio State University Wexner Medical Center, however, is placing its bets on gene therapy.

Gene therapy calls for delivery of an artificial micro-RNA that is able to silence the huntingtin gene. “The exact mechanism of Huntington’s isn’t perfectly understood, but the goal is to block that production of the mutant huntingtin protein,” says Dr. James

“Brad” Elder, who performed the clinicaltrial surgeries on two patients in June. “The assumption is that it’s the buildup of the protein that is doing cell damage.”

The procedure itself is minimally invasive, with no actual incision used. “This is so atraumatic that really it’s akin to starting an IV,” Elder says. “It’s just a bandage [that] holds things put for half an hour; then you take it off, and it’s like it never happened.”

Yet the promise of gene therapy to treat Huntington’s could be groundbreaking. “It will be several months before we have an understanding if this is working or not,” says Dr. Russell Lonser, also of the Wexner Medical Center. “But I think in this disease, like any deadly disease, where we’ve got a new type of platform to treat it, it’s always going to be exciting.”

And it could be a difference-maker not just for those already diagnosed with Huntington’s, but also those who have had a genetic test that indicates they may someday develop the disease. “If this proves effective in this patient population, well, why not do it earlier in the pre-manifest population?” Elder says.

Like brain disorders, cancer diagnosis and treatment is a field that sees constant advancement and refinement. Among physicians’ latest tools are a new style of mam-

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mogram that can produce MRI-level detail.

“Contrast mammo is a standard mammogram with the addition of intravenous contrast,” says Dr. Mitva Patel, a radiologist at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital.

While a traditional mammogram provides anatomic information alone, a contrastenhanced mammogram uses the contrast dye to provide a picture of blood flow through the veins in the breast tissue. “As cancers grow, they recruit blood vessels, and so that’s what we’re looking for,” Patel says.

“It shows areas of increased enhancement, or uptake, of blood flow to indicate that there is a cancer growing.”

Contrast-enhanced mammograms—which received FDA approval in 2011 but have only become more widely available in the last two years—are not normally used for annual screening purposes. At Ohio State, the exam can be done after a cancer diagnosis has been made. “Right after they get that diagnosis, between the time when they are seeing the breast surgeon, [we] offer them to come in for a contrast-enhanced mammogram,” Patel says. “That way we can determine the extent of disease.”

The technique may produce MRI-quality results, but it has one distinct advantage over MRIs: Contrast-enhanced mammograms are significantly less expensive, making them likelier to become available in communities that suffer from health care disparities. “Having something that performs similar to an MRI, at one-tenth of the cost, is something that can potentially serve populations better by making it more accessible,” Patel says.

Cancer treatment has become more effective and precise as cancer itself becomes better understood. “It’s basically the difference between normal grass and weeds when they grow and spread—that’s kind of the same concept of cancer growth,” says Dr. Sameh Mikhail of the Zangmeister Cancer Center. “Over the last few decades, different abnormalities in the DNA and other proteins in the cells … have been identified in some cancers as the main drivers of growth of the cells.”

Precision medicine, or targeted therapy, refers to orally or intravenously administered drugs that strike the specific proteins or genes in a tumor, thereby hobbling its growth. Another benefit: fewer side effects than those commonly seen in cancer treatment regimens like chemotherapy, says Mikhail, who likens chemotherapy to a “dirty bomb” that goes after cancer cells and nor-

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mal cells alike. “That’s why patients get side effects from chemotherapy.”

To know if a patient can benefit from precision medicine, doctors perform nextgeneration sequencing tests; the tests once required biopsies, but new technologies mean that a simple blood test now can suffice. “I look for certain mutations that have been shown to be main drivers of growth for that particular type of cancer,” Mikhail says.

“An example is a mutation called EGFR [epidermal growth factor receptor], which is, in the oncology community now, a well-known mutation and a well-established driver for growth of lung cancer cells.”

Advances also have been seen in traditional radiation therapy, which, the experts say, remains a vitally important component in cancer care. “We use it in a lot of different settings for a lot of different kinds of cancers,” says Dr. Timothy P. Cripe of Nationwide Children’s Hospital. “In the past, when we’ve tried to back off or get rid of it, we just don’t get a good result.”

At the same time, not all radiation therapy is created equal. Finding increasing acceptance is proton therapy, which uses focused protons (in lieu of the scattered electrons of an X-ray) to go after cancer cells while sparing healthy tissue. “The protons don’t penetrate the tissue as far,” Cripe says. “The energy gets dissipated, so the proton sort of goes in a certain distance and dies. … You can, basically in a three-dimensional space, conform the radiation energy delivery just to the tumor and minimize the side effects.”

While traditional radiation therapy still has a role—especially in total body radiation used to treat, for example, the bone marrow in a patient with leukemia—the reduction in side effects in proton therapy is a major advantage, particularly for young patients with long lives ahead of them. “Most of the long-term side effects are decades later in terms of cognitive decline, if you’re exposing brain, or organ function or bone growth defects,” Cripe says.

“Those issues, because they happen decades later, are most important in pediatric patients, who we’re wanting to cure for their lifetime.”

In partnership with Ohio State University, Nationwide Children’s will open the first proton therapy treatment facility in Central Ohio in 2023. All pediatric cancers can likely be treated using proton therapy, Cripe says.

“Especially brain cancer patients, because the brain is so important and sensitive to radiation,” he says. “The more we can precisely map things there, the better.”

Sometimes high-tech tools are deployed to deceptively low-tech ends. Such is the

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case with the efforts of physicians to create a nurturing, sensory environment for infants, especially those who have experienced certain complications. “We know that babies who are born preterm, or who have brain injury, have a really hard time developing the right way, or in a way where they can reach their full potential,” says Dr. Nathalie Maitre of Nationwide Children’s Hospital, adding that every preterm child is considered to be on a kind of brain-injury spectrum. “It turns out that, just because you’re born preterm, your brain has to face challenges that other babies don’t.”

For a preterm child, life outside of the womb is the very definition of a rude awakening; the sensory system that had been developing in utero is disrupted by “the machines, the noise, gravity, the sensations that have nothing to do with being cushioned inside the uterus in this watery, muscular environment,” says Maitre, who points to the

introduction of the touch and scent of parents—as well as the voice of mom or dad—as essential in making the infant’s environment as nurturing as possible. “There’s an active kind of listening that happens that allows the human brain, even the tiny, little human brain, to understand and start to process speech sounds,” she says.

In the case of preterm babies, speech can be introduced by making a voice recording of one or both parents and then allowing the child to “request” that voice—all while the child is still in the NICU. “Starting at right around 32 weeks … they can start to control their mouth actively,” Matire says. “We have a special air sensor that fits snugly on the end of a pacifier, and the baby then sucks on the pacifier. There’s a little Bluetooth that then sends a signal continuously, based on the baby’s suck strength and rhythm. … That determines how much of their mom’s voice to give them.”

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