Children Are Not Small Adults

SHARON H. FITZGERALD

Children Are Not Small Adults | Edward R.B. McCabe III,  nanopediatrics, Mattel Children's Hospital, Pediatric Research

Nanopediatrics Emerges to Ensure Nanotechnology Encompasses Kids

Imagine a pump the size of a molecule delivering medicine directly in the body where it's needed. Or a miniscule tool programmed to seek out and destroy the first cancer cells of a tumor. That's the promise of nanomedicine, medical applications in the much broader field of nanotechnology. Yet, as such customized medical innovations are being researched, Edward R.B. McCabe III, MD, has one reminder: Kids are different.

"I'm a pediatrician doing nanotechnology and nanomedicine, and one of the mantras in pediatrics is that children are not small adults," McCabe said. "So I began to think, 'You know, if we don't acknowledge right up front that we're doing nanomedicine on children, then people may forget that children are not small adults.' That's why we coined the term nanopediatrics." McCabe is a professor and executive chair of the Department of Pediatrics at UCLA's Mattel Children's Hospital in Los Angeles. Two years ago, under McCabe's leadership, Mattel launched the nation's first NanoPediatrics Program, focusing on the development and use of nanomedicine for the care of children. It remains the only specialized and solely dedicated program at an academic medical center in the United States, yet researchers at many other institutions are tackling the subject, and the breadth of research is growing.

In May, the journal Pediatric Research published its annual supplement for 2010, presenting research that its editors say "will form the basis of the emerging field of nanopediatrics." McCabe was the guest editor of the special supplement, and he wrote in the introductory article, "Nanotechnology and nanomedicine are anticipated to be major drivers of personalized medicine. It is essential that we focus the power of these technologies to enable personalized medicine for children, in a specialty of NanoPediatrics."

The papers in the special issue highlight the potential of molecular-level nanomedicine for children's health, and disease diagnosis is one example. The sequencing of the human genome has given researchers a laser-like view of how genetics contributes to disease development; thus, the detection of DNA sequence variations offers a powerful diagnostic tool for genetic-related conditions. UCLA research is honing in on a nanotechnology-enhanced detection of nucleic acids, and that paper is part of the Pediatrics Research package. Another paper focuses on molecular thermometry techniques that could recognize minute temperature changes at the subcellular level and help detect tumors or infections much earlier.

The research supplement also outlines combining diagnostic and treatment techniques, called theranostics. "Basically, it means that the nanoparticles are both therapeutic and diagnostic," McCabe explained. "For example, I study adrenal development. We haven't published this yet, but we're working on some nanoparticles that would go specifically to adrenal-cortical cells." The nanoparticles would first help enhance an MRI scan of carcinoma cells – and then release some sort of anticancer apoxic compound. "So when these things landed on the adrenal-cortical cells, they would also wipe out the cancer cells," he said, adding that several nanopediatric research initiatives are working to develop "smart bombs" that target specific tumor cells and leave the healthy cells alone.

Other papers in the special supplement outline more nanomedicine uses that may someday help treat children:

  • Nano-modified coatings to prevent infection of ventilator tubes in children.
  • Tissue engineering techniques to grow new organs, including bladders for children with congenital bladder dysfunction.

McCabe stressed that nanomedicine research must not ignore children's toxicity. "We don't fully understand why kids react to drugs differently than adults do. It's an area of nanotoxicology, and the concern was that if we don't really look at toxicity in kids, then we might have them react differently to the nanoparticles than adults," he said.

McCabe has a doctorate in pharmacology, and he said, "If you had asked me back in the late 1960s or early '70s, when I was getting my PhD, about side effects, I would have said each of us has a 5 percent risk of this side effect or a 10 percent risk of that side effect. I think we're learning more and more that, no, that's not the case. It's not purely probabilistic, but some of us have variations in our genome that predispose us to the side effects. We're beginning to understand that." With children, the predisposition may be more profound, he added.

McCabe said the Mattel NanoPediatrics Program offers seed grants to researchers to help get their research off the ground. "The NIH gives you money for research you've already done. What that means is that you have to have strong pilot data when you go in. What I was hoping to do was prime the pump for some NIH grants by giving these $20,000 to five investigators and let them get preliminary data, and then write an NIH grant," he said. The strategy has worked, he added, and the program is thriving.

Thus, McCabe is moving on. He recently accepted a position as executive director of the Linda Crnic Institute for Down Syndrome at the University of Colorado School of Medicine. "Advances to be made on the research side and translating those into clinical improvements with Down Syndrome and other disorders that have been considered intractable in the past will be through personalized medicine. So I really see this as an opportunity to refocus," he said.

Yet more promises for his specialty of nanopediatrics.