Science Translational Medicine: Monkeys with Parkinson’s Treated Using Gene Therapy

A French research team reports a new gene therapy approach tested in macaque monkeys that shows promise for treating Parkinson’s disease by restoring dopamine in the brain and preventing the jerky, involuntary movements that accompany long-term treatment of the disease.

The research is reported in the 14 October issue of Science Translational Medicine, the new journal from AAAS and Science that’s designed to help speed basic research-advances into clinics and hospitals worldwide.

In Parkinson’s disease, loss of the chemical dopamine causes lack of control over body movement. Standard treatment includes giving patients oral drugs that briefly increase the amount of dopamine in the brain. Yet this treatment fails to maintain stable levels of dopamine required for normal function, and leads to movement disorders called dyskinesias. Their results demonstrate that using gene therapy to restore dopamine in the brain has the potential to correct Parkinson’s disease in patients without the complications of dyskinesias.

To simulate advanced Parkinson’s disease, lead author Bechir Jarraya and colleagues gave monkeys a neurotoxin that selectively causes the condition until the animals developed bodily tremors, rigidity, and the unstable posture characteristic of severe Parkinsonian syndrome.

The researchers then inserted three genes critical for producing dopamine into the brains of the monkeys, to treat the induced Parkinson’s. To measure dopamine in the brain, biological probes were placed into the brains of the monkeys, and the team observed the animals for up to three-and-a-half years. They found that that this gene therapy approach safely restored concentrations of dopamine in the brain, corrected motor deficits, and prevented dyskinesias—without any severe adverse side effects. The authors report that a phase 1/2 human clinical trial using the same dopamine gene therapy approach is currently in progress.