Gene-based therapy successful in Parkinson's disease

Nov 20 2007

Brain scans have revealed that the first gene-based therapy for Parkinson's disease was effective.

Gene therapy has never before been used to treat a degenerative brain disease in humans and the success represents an important landmark.

For the study scientists at the New York University School of Medicine injected the brains of Parkinson's patients with a harmless virus which was genetically modified.

The virus carried a human gene which dampens down the nerve cells that become overactive in Parkinson's patients which as a result interferes with movement control.

Position emission tomography (PET) scans were carried out before the surgery and repeated six months later and then again one year after the surgery.

The PET scans revealed how the activity of different brain circuits changed before and after treatment and confirmed the treatment worked by highlighting brain circuits involved in movement that had recovered; a significant improvement was also noted in the patients.

The brain scans were part of the treatment in the on-going trial which involved eleven men and one woman.

The patients received the injections directly into part of the brain most affected by the disease and the scans later showed that some brain circuits that act abnormally in Parkinson's patients were working healthily again.

The genes were delivered to only one side of the brain to reduce risk and to better assess the treatment.

Signs of recovery were seen one month after treatment, and three to six months later all showed on average a 30% improvement in their movement; one patient in particular astounded the doctors, after tests showed his movement had improved 65%.

Dr. David Eidelberg, who led the study says the scans show that the treatment corrects abnormal activity in the brain, which in itself shows the therapy works.

Dr. Eidelberg says before the patients' brains were scanned it was unclear whether their recovery could be explained by the placebo effect, or even by the surgery to enable doctors to inject the gene-based drug into their brains.

However a detailed examination of the scans showed very specific changes in the patients' brains that could only be explained by the therapy, says Eidelberg.

Parkinson's disease affects millions of people worldwide; symptoms, such as tremors, difficulty in moving and muscles that tighten and lock, usually appear when a person is over 50.

There is no cure for the disease and while several drugs are available to treat symptoms, some patients experience side-effects, among them a condition called dopamine dysregulation syndrome.

Patients affected by this effect need increasing doses of medication and become prone to aggressive outbursts and indulge in risky behaviour.

Parkinson's disease is caused by a loss of nerve cells in one part of the brain where the cells release a chemical called dopamine; this allows messages to be sent to parts of the brain that coordinate movement and as the dopamine-producing cells die off, these parts of the brain stop functioning properly.

Along with this levels of another chemical messenger, which dampen down over-active cells, also begin to drop and it is these chemical levels which were boosted in the trial.

The team are now planning a second, larger trial of the therapy, due to begin early next year which is expected to last 18 months.

The study is published in the current issue of the journal Proceedings of the National Academy of Sciences.