Sending Genes into the Brain

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As with DBS, surgeons first drill a small hole in the skull, then insert an electrode to search for a small brain area called the subthalamic nucleus, which emits a characteristic pattern of electrical activity. But the electrode is then removed, and a small catheter is inserted, and a small pump infuses the genetic material into the brain. The specialized drug-delivery device was developed by Medtronic, a medical-device company that also markets DBS systems. Mordock says that Neurologix plans to market the device and the gene-therapy treatment together.

In a small trial in which every Parkinson's patient received the same treatment, they showed a 29 percent improvement in motor function. Researchers have begun a larger, blinded trial and expect to have preliminary results later this month.

A second approach is to use gene therapy to slow or prevent cell death in the brain area ravaged by Parkinson's. Federoff is overseeing an academic consortium planning human tests of a gene therapy that codes for a protein called GDNF (glia-derived neurotropic factor), which enhances neuronal survival. The therapy is also delivered via a catheter in the brain, but the infusion is driven by a small pressure gradient, a technique known as convection-enhanced delivery. Federoff, who is also the founder of Canadian startup MedGenesis Therapeutix, which is commercializing the technology, says that this allows for more-targeted delivery.

In addition to convection-enhanced delivery, surgeons will use real-time neuroimaging to make sure that the gene therapy is delivered as precisely as possible. Scientists can add a labeled marker to the gene-therapy solution, which can then be seen on CT or MRI scans and used to visualize the diffusion of the molecules in the brain. Researchers have already used this technique to deliver therapies to patients with brain cancer.

In addition to cancer, Parkinson's disease will likely be the first to be treated using these approaches: scientists know which part of the brain is most damaged and can design therapies accordingly. (Alzheimer's disease, in contrast, has a much more diffuse effect on the brain.)

Success with Parkinson's could pave the way for treating other disorders. "As we learn more about the biology of these disorders and develop more treatment compounds, opportunities will expand with the ability to deliver drugs locally," says Russell Lonser, chair of the Surgical Neurology Branch of the National Institute for Neurological Disorders and Stroke, in Bethesda, MD.

Gene therapy does have its downsides compared with DBS, however. "DBS can be turned off, catheters can be removed, and patients can then be brought back to their basal state," says Federoff. "We believe that gene delivery is lifelong."