Biological pacemaker created by gene transfer

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    Added gene keeps guinea-pig hearts beating to time.

    Each year about 600,000 operations worldwide implant electrical pacemakers Credit: © Getty Images

    Researchers have fixed heart pacemakers with gene therapy. If the treatment, tested in guinea pigs, works in humans, biological pacemakers might offer a cheaper, safer alternative to electronic implants.

    The cells that keep the heart beating regularly can die or become disconnected as people age. Each year about 600,000 operations worldwide implant electrical pacemakers that stimulate the heart. Batteries must be replaced, at further risk and expense, every 5-10 years, and patients must avoid strong magnetic fields, such as metal detectors and some medical scanners.

    The new approach instead adds a gene that changes the flow of chemicals in and out of heart cells. This flow turns ordinary cells into pacemakers, by creating an electrical charge1.

    Pacemaker cells provide an electrical jolt that starts the heartbeat and controls its rhythm. In the embryo, every heart cell has pacemaking power. In adults this is suppressed in all but a small patch of cells where the heartbeat begins.

    Cardiologist Eduardo Marbán of Johns Hopkins University in Baltimore, Maryland, and his colleagues suppress this suppression. The team disrupt a protein that pumps positively charged potassium ions into heart cells. Using a virus they deliver a gene that encodes a specially designed version of one of the protein's segments.

    When the cell builds the introduced protein into its potassium pumps, they stop working. This creates a negative electrical charge inside the cell, which spreads over the heart and creates rhythmic contraction.

    "You'd only need to modify several thousand cells," says Marbán. "The amount of virus and gene needed would be very small." In future, genetic manipulation of individual cells could treat many other heart defects as well as failed pacemakers, he says.

    “There's a mountain range to climb before this technique could be used in people Mark Boyett , University of Leeds”

    Cardiologist Mark Boyett of the University of Leeds, UK, agrees, but adds that "there's a mountain range to climb" before this technique could be used in people. Other genes may need to be manipulated to create a fully functioning pacemaker from regular heart cells or to fix damaged pacemaker cells.

    And the treatment would have to be carefully targeted. Creating small pacemakers across the heart would give a chaotic heartbeat. "It's a recipe for fibrillation and death," says Boyett.

    The US team plans to move onto trials in pigs, where small groups of heart cells can be modified by injection or by releasing the virus close to them. Marbán hopes that a human treatment might be available in about four years. This is "a little bit optimistic", according to Boyett.

    References

    1. 1

      Miake, J., Marbán, E. & Nuss, H. B. Biological pacemaker created by gene transfer. Nature, 419, 132 - 133, (2002).

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    Biological pacemaker created by gene transfer. Nature (2002) doi:10.1038/news020909-7

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