Clinical Trials and Parkinson Disease

Wellness Series Summary – Clinical Trials 

Speaker: Paul Larson, MD 

Below is a summary of the presentation 

Biological Approaches to Surgery for Parkinson’s Disease 

Despite adjustments in medication, Parkinson’s disease progresses, and individuals may experience worsening motor function including on/off periods or dyskinesia. This may lead an individual to turn to surgical options. Deep brain stimulation (DBS) is currently the gold standard surgical treatment for Parkinson’s disease however it has its disadvantages. DBS is a symptomatic therapy meaning it treats the symptoms and does not alter the brain biology or stop the progression. It is a hardware-based treatment which includes the risk of complications such as infection, erosion, and migration. It is dependent on the battery which needs to be surgically replaced or recharged. It can also be time consuming to have the settings adjusted. 

Cell Transplantation 

For many years, biologic treatments have been considered for Parkinson’s due to how it affects a very specific part of the brain. One idea is to transplant new brain cells to the area where cells are dying. The problem with cell transplantation is where to get these cells from. One thought was to harvest cells from the adrenal glands, but it was unsuccessful. Another option was to use fetal cells but ethically there were some issues and placebo-controlled trials failed to show benefit. These studies showed that cell transplants can be done and that a proportion of the cells survive, but significant issues and questions remain. One is how our immune system will respond to the foreign brain cells and the high doses of immunosuppressant medications that would be required. Other questions are how well the cells would disperse and integrate into the local network.  

Gene Therapy 

Another way to alter the brain biology is gene therapy. Gene therapy uses an inactivated virus to transport “good” genes into the brain for a specific part of the brain to have a new biological function. A virus can be manipulated to inject DNA into a cell to alter a cell’s function so it can do something positive such as produce more dopamine. The virus then detaches and dies.  

Adeno associated virus (AAV) is a virus that is naturally occurring and not known to cause disease. When placed into the CNS, it doesn’t trigger a large immune response. It also has a strong affinity to neurons. 

Amino acid decarboxylase (AADC) is an enzyme that converts levodopa to dopamine in the brain. As PD progresses, the amount of AADC in the brain continues to drop making medications less effective.  

A phase 1 study using AAV carrying the genetics for AADC showed improvement in motor scores when individuals with PD were on and off medications. Imaging also showed the brain was producing more dopamine.  

Goals for gene therapy is to make the procedure less invasive and more effective using imaging, better delivery techniques, and improved infusion strategies.