The first attempt to treat Parkinson鈥檚 disease with gene therapy reduced symptoms by as much as 70%, researchers say.
Patients received single injections into their brains of a harmless virus that delivered genes to relieve the condition.
鈥淭here was a 25% to 30% improvement in the symptoms of all recipients,鈥� says Matthew During at Cornell University in New York, US, who led the team that carried out the experimental procedure on 11 men and one woman. Some patients on higher doses did even better, with improvements of up to 70%.
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鈥淲e must be cautious, but we鈥檙e very encouraged by these results,鈥� says During. 鈥淚t鈥檚 one of the biggest successes of gene therapy so far.鈥�
The team injected the viruses into a part of the brain called the subthalamic nucleus, which becomes overactive in patients with Parkinson鈥檚 disease.
Gene delivery
Such overactivity puts strain on neurons that produce the neurotransmitter dopamine, which is vital for movement control. As a result, patients with Parkinson鈥檚 disease have depleted dopamine levels.
One reason the subthalamic nucleus is overactive is that it underproduces another neurotransmitter called gamma-aminobutyric acid (GABA).
To redress this and dampen activity in the subthalamic nucleus, During used harmless, cold-like viruses to deliver genes that ramp up the production of GABA. These extra genes code for an enzyme that converts the amino acid glutamate into GABA.
The team injected the patients鈥� subthalamic nuclei directly, using a drop of fluid containing up to 35 billion viral particles.
Only one hemisphere of the patients鈥� brains received the treatment 鈥� each hemisphere controls movement in the opposite side of the body, so the untreated half of the brain would act as a control to determine how successful the therapy was.
Unforeseen benefits
The effects of the treatment became apparent about three months after the injections about three months after the injections, mainly producing improvements in the expected side of the body. But to the researchers鈥� surprise, there were also improvements in the side of the body corresponding to the untreated hemisphere too.
鈥淚t is now four years since the first patient was treated, and he鈥檚 now riding his bike,鈥� says During. 鈥淲hen we first met him, he couldn鈥檛 even hold a glass of water.鈥�
During says that such a simple, one-off procedure has advantages over deep brain stimulation, a widely-used electro-mechanical method of dampening activity in the subthalamic nucleus.
In this process, patients are implanted with electrodes that control the brain region by delivering electrical impulses. But these have complications, such as infections associated with the implant, batteries running out of power, and the physical inconvenience of electrical leads.
Placebo effect?
Others are sceptical of the team鈥檚 findings. 鈥淚 think there is sufficient promise that a proper trial of this technique is justified,鈥� says Jon Stoessl, who scans the brains of Parkinson鈥檚 patients at the University of British Columbia in Vancouver, Canada. 鈥淏ut how do they know the virus stays in the areas they want?鈥�
Stoessl acknowledges that the symptoms did improve, but says that patients with Parkinson鈥檚 disease are notoriously prone to placebo effects, showing improved symptoms simply because they have high expectations of treatment.
Stoessl also speculates that dampening, or damage to the subthalamic nucleus, might have the side-effect of damaging the known function of this area of the brain in learning. He says that this criticism would apply equally to deep brain stimulation.
Journal reference: The Lancet (vol 369, p2097)
