VEGF-B - A New Neurotrophic Factor for Treatment for Parkinson's Disease

Objective/Rationale: 
We discovered that the vascular endothelial growth factor, VEGF-B, acts as a natural response of brain cells to a neurotoxin that produces Parkinson’s disease in pre-clinical models. VEGF-B also was neuroprotective in a culture model of Parkinson’s disease. We hypothesize that further supplementing the amount of VEGF-B in the brains of people with Parkinson’s disease could serve to slow or halt the disease process, and propose to begin testing the feasibility of this approach using pre-clinical models.

Project Description: 
We will test if strengthening the natural protective response seen in culture by adding exogenous VEGF-B may have the potential to be a disease modifying therapy in a pre-clinical model of Parkinson’s disease. We will inject VEGF-B into the brain and test this in a model treated with a neurotoxin (6-hydroxydopamine) that mimics Parkinson’s disease. We plan to further investigate the neuroprotective and neurorestorative potential of VEGF-B, by comparing it to GDNF, the gold standard neurotrophic factor for Parkinson’s disease research. We will evaluate the effectiveness by looking at movement symptoms with a battery of behavioral tests and counting the number and connectivity of dopamine-producing brain cells. We will evaluate the ability of VEGF-B to both protect against neurotoxin and restore neurotoxin-induced damage.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
This project is directed at developing a novel approach to neuroprotective treatments for Parkinson disease. To date, most of the current studies testing neurotrophic agents have used members of the GDNF-family of growth factors as test agents; these are protein molecules related to “glial-derived neurotrophic factor” (GDNF). If our study is successful, VEGF-B could be added to the list of neuroprotective and/or neurorestorative factors, and further optimized as a novel gene therapy approach.

Anticipated Outcome: 
After completion of this work we will be able to either validate, or disprove VEGF-B as a new target for therapeutic development in Parkinson’s disease. If validated we would then propose to make a standard type of gene therapy vector (an engineered virus that safely delivers genes to the brain) that will increase the levels of VEGF-B in the affected area in the brain, and test long-term efficacy and safety of this treatment.