Breaking Barriers

  • Photo by Sergey Anatolievich Pristyazhnyuk; copyright Getty Images
    Photo by Sergey Anatolievich Pristyazhnyuk; copyright Getty Images

    Though the Center for Nanomedicine is part of the Wilmer Eye Institute, the research is by no means restricted solely to the eye. Researchers at the center are actively working in many therapeutic directions including neurological disorders. One of the most promising is a post-natal treatment for cerebral palsy. According to the Centers for Disease Control, cerebral palsy is the most common motor disability in childhood, with symptoms ranging from imbalance to severe motor impairment requiring lifelong care. The husband-wife team of Kannan Rangaramanujam, a professor of ophthalmology, and Sujatha Kannan, an associate professor of anesthesiology and critical care medicine, is using nanomedicine to “rescue” rabbit babies—known as kits—that suffer from cerebral palsy. Hanes notes that video taken of the kits “is pretty dramatic.” “The untreated kits are essentially inactive and unable to move with normal balance and coordination, while the treated kits appear near normal, hopping and walking around,” he says.

    In the Kannans’ model, cerebral palsy is induced by maternal inflammation, a common cause of the disease in humans. This leads to fetal neuroinflammation, caused by activated microglia and astrocytes, which normally provide immune defense in healthy brains. When inflamed, however, these cells go rogue—causing significant collateral damage in the brain.

    The anti-inflammatory drug NAC is believed to be effective against such inflammation, but it has trouble penetrating deep into the tissues to target cells in the brain, and thus has not been effective in treating cerebral palsy, even at large doses. Nanomedicine can modify existing drugs like NAC and deliver them to target cells in a Trojan horse manner. The Kannans have shown that attaching NAC to small, tree-like polymers called dendrimers can help NAC make it across the blood-brain barrier and into inflamed tissues and cells. In an ironic twist, they believe that the same inflammation that causes cerebral palsy also weakens the blood-brain barrier, allowing for the increased uptake of dendrimers. “This enhanced permeability of the blood-brain barrier may also allow free-form NAC into the brain, too, but the drug is distributed non-specifically, and doesn’t efficiently enter the target cells. We believe that packaging NAC in dendrimers helps it move nicely through the brain,” says Kannan Rangaramanujam.

    The duo showed that a single dose of their dendrimer-based NAC can relieve neuroinflammation and lead to significant improvements in motor function in treated kits, even more than those receiving an order of magnitude higher concentration of dendrimer-free NAC, which showed no effect. The work was published in 2012 in the journal Science Translational Medicine. “This suggests a new window of opportunity has been opened for the treatment of cerebral palsy in humans and, perhaps someday, the possibility of preventing cerebral palsy altogether,” Kannan says. He notes also that similar inflammation has been implicated in diseases ranging from autism to multiple sclerosis, holding the hope of treating those diseases as well.

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