Parkinson’s and gene therapy

Dr. Deborah Young, Assoc. Prof & Head of Molecular Neurotherapeutics at the Centre for Brain Research

My lab is interested in developing new treatments for Parkinson’s disease. One of the approaches we are developing is a technology called gene therapy. What’s a gene? Well, every cell in your body (except for red blood cells) has an entire copy of your DNA, the unique blueprint that makes us who we are.

Genes are short segments of DNA and they carry the specific instruction code for the many different proteins that are the building blocks for the cells in our body. Different cells make different sets of proteins - that’s what distinguishes different cells in your body, for example, why a brain cell is different to a heart cell.

Gene therapy involves inserting healthy copies of genes into a cell to replace a faulty one or to put in genes that alter the behaviour of the cell in order to produce a beneficial effect for the patient.

In Parkinson’s the cells that produce dopamine are progressively dying. An example of a gene therapy strategy might be to introduce a gene that codes for a protein capable of boosting the resistance of cells that are destined to die, to protect them from whatever it is that is attacking them. To prevent the body rejecting these introduced genes they are delivered via delivery vehicles called vectors.

Different gene therapy strategies have been tested in research labs. One technique that was trialed in a small group of people with Parkinson’s involved introducing a synthetic copy of a gene called GAD (glutamic acid decarboxylase) which is an enzyme involved in producing GABA, a brain chemical that is the main inhibitor in the brain. It calms the cells in the subthalamic nucleus that have become over-excited from being deprived of dopamine.

The criteria for enrolment in the trial and the surgical procedure itself were similar to those used in deep brain stimulation. The procedure was safe, and there were no adverse side-effects associated with the gene therapy. The gene therapy didn’t make the Parkinson’s symptoms worse, and some of the patients showed a small improvement in function on the side that received the treatment. The success of that trial was extended to a second gene therapy trial in another group of Parkinson’s patients with encouraging results.

This work is still in the testing phase, and it might be a few years before doctors can offer gene therapy treatments to their patients but gene therapy could provide another alternative or complementary approach to existing drug and surgical treatments for Parkinson’s disease.