Parkinson's Researchers Study New Drug-Delivery Method

LEXINGTON, Ky. (Nov. 9, 2009) − A  team of Parkinson's disease researchers at the University of Kentucky is investigating a promising method for delivering therapeutic drugs directly to patients' brains through an implanted catheter connected to a small, portable pump.

The research, funded by the Michael J. Fox Foundation and the Kinetics Foundation, is being led by Peter Hardy, assistant professor of anatomy and neuorbiology, and Luke H. Bradley, assistant professor of anatomy and neurobiology, and of molecular and cellular biochemistry, in the UK College of Medicine.

"A variety of diseases affecting the brain cannot be treated effectively with drugs because the brain is protected by the blood-brain barrier –a special barrier separating it from the blood vessels," Bradley said. "This method circumvents the blood-brain barrier and enables the direct and measured delivery of promising drugs directly to the areas of the brain most affected by Parkinson’s disease."

The research uses experimental surgical techniques developed by Dr. Zhiming Zhang, a UK associate professor of anatomy and neurobiology.  Zhang has developed a strong program in experimental neurosurgery focused on site-specific delivery of therapeutic drugs into the brain. His methodology has broad potential application for treating a number of neurological disorders, including Parkinson's disease.

This method has previously been used to deliver therapeutic compounds, such as GDNF, to the brains of Parkinson's disease patients in several clinical trials, including a Phase 1 clinical trial organized by UK's Morris K. Udall Parkinson's Disease Research Center of Excellence. While some of these clinical trials showed moderate success in the remission of symptoms, others did not. The mixed results may have stemmed from the difficulty of dosing the target tissue adequately, Bradley says.

"Our knowledge of the movement of molecules in the brain is incomplete, so scientists and clinicians must resort to approximations and 'educated guesses' to predict the infusion protocol to achieve a therapeutic dose to the entire target tissue," Bradley said. "In addition, the infusion protocol is dependent on the properties of the molecule – including its size, solubility, resistance to degradation, and bioactivity in the brain."

The current research aims to develop methods of using  magnetic resonance imaging to measure the distribution of  two experimental drugs in the brain, Hardy said. Results from this work will improve the effectiveness of direct delivery of therapeutic compounds for Parkinson's disease by improving the prediction of infusion parameters appropriate for molecules of different pharmacologic and chemical characteristics, Bradley said.