Gene therapy for Parkinson’s disease has moved a step closer to acceptance in the wake of its first successful double-blind clinical trial.

In 2007, Andrew Feigin of the Feinstein Institute for Medical Research in Manhasset, New York, and colleagues conducted an open-label trial – one in which both patients and researchers know which trial members are receiving the treatment and which are given a placebo – to assess a new gene therapy for Parkinson’s, which is a neurodegenerative disorder. They demonstrated that a gene that codes for glutamic acid decarboxylase (GAD) can improve the condition of people with the disease when injected into their brains.

GAD is an enzyme that catalyses production of an inhibitory neurotransmitter called gamma-aminobutyric acid (GABA). Typically, people with Parkinson’s produce too little GABA, and consequently have overstimulation in an area of the brain called the subthalamic nucleus. This overactivity in turn puts strain on neurons that produce another neurotransmitter – dopamine – which is vital for movement control. This helps explain some of the symptoms of Parkinson’s, which include tremors, sluggish movements, rigid muscles and impaired posture and balance.

Now the team have put their therapy to the ultimate test: a double-blind clinical trial in which neither the patient nor the clinical staff – other than the surgeons performing the procedures – knew who was receiving the therapy and who was given a placebo.


Hole in the head

Feigin and his team recruited 65 people with Parkinson’s. Twenty-three of them received true gene therapy: the researchers drilled through their skulls and injected a virus carrying the gene that codes for GAD. Twenty-two other patients received only injections of saline solution beneath the scalp in a sham procedure designed to give patients the impression that they had received surgery.

One, three and six months later the researchers measured the severity of the patients’ symptoms. Those who had received gene therapy showed improvements in their motor functions of 23.1 per cent, on average, according to a standardised rating scale – those in the sham brain surgery group improved by just 12.7 per cent.

“Not only is gene therapy a very novel treatment,” says Feigin, “but in this study it was safe and well-tolerated. That to me is a big deal that really opens up the field.”

Stéphane Palfi at the University of East Paris Créteil Val de Marne, France, agrees that the safety issues are most important. He also points out that the improvements are relatively mild compared with some existing treatments, such as sending electrical impulses into the brain using deep brain stimulation.

He says we need to wait for long-term studies to determine whether gene therapy is ultimately a better approach than those other therapies.

Journal reference: The Lancet Neurology, DOI: 10.1016/s1474-4422(11)70039-4