The tremors in individuals with Parkinson's disease are caused by excessive activity in the areas of the brain that control muscle activity. The key damage in the disease is the loss of a specific group of nerves that control muscles, so most therapies have focused on replacing this missing activity. But researchers are reporting success with using gene therapy to rewire the brain to work around the lost nerve cells.
The idea behind the new therapy comes from the recognition that the missing nerves take part in a complex web of both stimulatory and inhibitory connections that, combined, regulate muscle activity. A key player in that network is a structure called the subthalamic nucleus, which sends stimulatory signals on to other areas of the brain. In people with Parkinson's, this structure receives fewer inhibitory signals and becomes overactive, triggering tremors.
The research team used gene therapy to convert the signals from the subthalamic nucleus from stimulatory to inhibitory. Into this structure they injected a virus engineered to produce an enzyme that generates a nerve inhibitor. Thus, cells infected with the virus were converted from activators to inhibitors of the nerves they signalled to.
People receiving the therapy showed no adverse reactions for up to a year after injection. Over the course of several months, their scores on tests of Parkinson's symptoms gradually improved. With the safety of the procedure established, larger-scale test are planned.
Image credit: John Wildgoose
Kaplitt MG et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 2007;369(9579):2097-105. Abstract