Researchers Study Technologies To Deliver Drugs To The Brain

The research team is led by Greg Gerhardt, Ph.D., professor, and includes Don Gash, professor and chair, and Zhiming Zhang, M.D., assistant professor, all in the Department of Anatomy and Neurobiology, UK College of Medicine.

The research will concentrate on modifying the Medtronic SynchroMed® Infusion System, an implantable and programmable pump developed by Medtronic Inc., to deliver drugs directly into the brain. The pump currently is approved for delivery of drugs directly to the fluid around the spinal cord in patients with chronic and intractable pain, cancer pain, and severe muscle spasticity, as well as the delivery of chemotherapy agents to treat colorectal cancer that has spread to the liver.

In support of this research program, the team at the UK College of Medicine has received a five-year, $5 million grant from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, to establish a Parkinson's Disease Research Center of Excellence. Only eight centers were funded this year, bringing the total number funded to 11 nationwide.

The Parkinson's Disease Research Centers of Excellence program was developed in response to Senate Bill 535, also known as the Udall Bill in honor of former Congressman Morris K. Udall who died in December 1998 after a long battle with Parkinson's disease. All the centers will be named Morris K. Udall Parkinson's Disease Research Centers of Excellence.

In accordance with these federal requirements, UK will recommend to its Board of Trustees that the center be named the Morris K. Udall Parkinson's Disease Research Center of Excellence.

Parkinson's Disease Research Centers of Excellence at Emory University, Massachusetts General Hospital and The Johns Hopkins University School of Medicine were funded in 1998. The eight new centers are located at the UK College of Medicine; Brigham and Women's Hospital Center for Neurologic Diseases in Boston, Mass.; the Neurological Institute at Columbia University; the University of Virginia Health System; the Mayo Clinic in Jacksonville, Fla.; Duke University; the University of California at Los Angeles; and Harvard Medical School and McLean Hospital.

"We are confident that knowledge of the fundamental processes underlying this debilitating disease will, in turn, lead to improved diagnosis and treatment," said Gerald Fischbach, M.D., director of the NINDS. "The centers' multidisciplinary framework provides the collaborative environment necessary to take full advantage of emerging discoveries in the basic and technological sciences that are the prelude to clinical advances. It is my hope that the scientists at the different centers will work together whenever possible."

Initially, the UK College of Medicine researchers will work with a protein called glial cell line-derived neurotrophic factor (GDNF), developed by Amgen Inc. GDNF is a natural growth factor found in low levels in the adult human brain. It has been shown in preclinical studies to protect dopaminergic neurons in the midbrain. The destruction of these neurons causes the symptoms of Parkinson's disease. In these studies, GDNF also has shown promise in protecting these neurons from cell death and in stimulating improved function.

Use of this technology will not be limited to this one compound. The drug delivery system will be applicable to a range of drugs that need to be delivered to the brain.

The advantages of this technology are that the compounds will bypass the blood-brain barrier that is very difficult for many compounds to cross and that side effects will be minimized as the compounds will be delivered only to the areas with degenerated tissue.

Currently, this research is in the preclinical stage. No trials in humans are in progress.

Along with research and development, the program will have training and outreach components. The team plans to recruit one graduate student and two postdoctoral fellows. The team also will interact closely with local community support groups for Parkinson's disease.

According to the NINDS, Parkinson's disease affects more than 500,000 Americans. It is a neurological disease, most often of older people, that progressively impairs control of body movement and often leads eventually to rigid immobility. Symptoms of Parkinson's disease include tremors, stiff limbs, slow or absent movement, lack of facial expressions, a shuffling gait and a distinctive stoop. Depression and an impaired ability to think also may develop. These symptoms result from degeneration of nerve cells in the brain that produce the chemical dopamine.

Although treatment with the drugs levodopa and carbidopa almost can completely restore normal movement to many with early Parkinson's disease, the treatment gradually loses effectiveness as the disease progresses.

"We expect clinical treatments based on the targeted delivery of drugs to specific sites in the brain to becoming increasingly commonplace over the next decade," Gerhardt said. "Our research team at the UK College of Medicine is pioneering the next generation of treatments for Parkinson's disease."