Together, the findings suggest that gene therapy to enable the brain to retain its ability to produce dopamine, a neurotransmitter that falls in critically short supply in Parkinson’s patients, could be safely attempted during earlier stages of the disease with an added likelihood of success.

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“We have worked every day for 10 years to design a construct to the gene delivery vector that enhances the safety profile of gene transfer for Parkinson’s disease,” said Ronald Mandel, a professor of neuroscience at UF’s McKnight Brain Institute and the Powell Gene Therapy Center. “With that added measure of safety, we believe we can intervene with gene transfer in patients at earlier stages of the disease. We strongly believe that trials to save dopamine-producing connections in patients with Parkinson’s disease have failed because the therapy went into patients who were in the late stages of the disease and who had too few remaining dopamine-producing connections.”

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“With this technique, you could adjust the therapy in the patient,” said Fredric P. Manfredsson, a postdoctoral associate in UF’s department of neuroscience. “That would be extremely helpful because no one is really certain yet what dosage is required for a protective effect in humans. The process is also much more sensitive than we had imagined it would be. GDNF production can be shut down completely with a dose of doxycycline that is much smaller than what is commonly prescribed.”

A growth factor used in clinical experiments to rescue dying brain cells in Parkinson patients may cause unwanted weight loss if delivered to specific areas of the brain, according to University of Florida researchers in the March online edition of Molecular Therapy.

The discovery is a cautionary warning for experimental treatments to treat Parkinson’s disease that use GDNF, short for glial line-derived neurotrophic growth factor.

In addition, the finding broadens understanding of the brain’s role in the regulation of metabolism and body weight, suggesting that gene therapy techniques in the brain potentially could control obesity.

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Doctors may be able to tailor a specialized form of brain surgery to more closely match the needs of Parkinson patients, according to results from the first large-scale effort to compare the two current target areas of deep brain stimulation surgery, or DBS.

Called the COMPARE Trial, the National Institutes of Health-funded study conducted at the University of Florida evaluated 45 patients for mood and cognitive changes related to DBS. UF investigators found that DBS in either brain target effectively treated motor symptoms such as tremors, stiffness and slowness. However, DBS also produced unique effects depending on the target location, especially in patients’ moods and mental sharpness.

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