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Funded Studies

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.
 

Final Outcome

After previously discovering 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, we now tested 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. In a 1st experiment we injected VEGF-B into the brain and tested this in pre-clinical models treated with a neurotoxin (6-hydroxydopamine) that mimics Parkinson’s disease. We evaluated the effectiveness by looking at movement symptoms with a battery of behavioral tests and counting the number and connectivity of dopamine-producing brain cells. VEGF-B was shown to be protective against the neurotoxin, it reduced behavioral deficits and partially protected neurons and connectivity. We are currently analyzing a 2nd experiment that tests the effectiveness of VEGF-B directly to GDNF, the gold standard neurotrophic factor for Parkinson’s disease research. Preliminary behavioral data support a modest neuroprotective effect by VEGF-B that was statistically not different from the effect of GDNF. We will further test if VEGF-B is also able to restore neurotoxin-induced damage, as has been shown by GDNF.

 

Presentations & Publications

Report (and include copies of) any presentations, abstracts, findings, or papers (submitted for publication, in press, or published) that resulted from the work made possible by this award.

 

Abstracts

Sherman S.J., T. Falk, S.L. Zhang and X. Yue (2010) Vascular Endothelial Growth Factor-B186 improves motor behavior in vivo in a rat model of Parkinson’s disease. Movement Disorders 25, Suppl. 3: S723-S723


Researchers

  • Torsten Falk, PhD

    Tucson, AZ United States


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