Greg Gerhardt, Ph.D., professor, Department of Anatomy and Neurobiology and Department of Neurology, director of the Morris K. Udall Parkinson's Disease Research Center of Excellence, and director of the Center for Sensor Technology, has headed the Udall Center at UK since its inception six years ago. As one of only 12 Udall Centers in the nation, UK's center represents the leading edge of research into Parkinson's disease, which at this point remains an incurable condition.
GDNF differs from other Parkinson's therapies in that it has demonstrated potential to halt or perhaps reverse the neurodegenerative condition. Current treatments only provide temporary relief from symptoms.
"The NINDS is pleased to continue the support of the University of Kentucky Udall Center, a unique component of the Udall center program that provides non-human primate studies of potential therapeutics in Parkinson's disease," said Diane Murphy, Ph.D., Program Director for the NINDS' Morris K. Udall Parkinson's Disease Research Centers of Excellence.
Gerhardt and colleagues will spend the next five years investigating potential negative effects of GDNF, and how to fine tune dosing and administration techniques to make the therapy a safer and more viable alternative.
The $6 million funding from NIH represents a vote of confidence for the UK Udall Center and its work to date on GDNF and related molecules. At the end of this five-year funding cycle UK researchers plan to be ready to move GDNF or a related compound once again into human clinical trials – a timetable considered ambitious by industry standards, but realistic to Gerhardt.
UK's research into GDNF made headlines recently when the CBS news show "60 Minutes" broadcast a feature on the controversy that arose when Kentucky and New York patients enrolled in a national Phase 1 clinical trial for the drug were left without medical treatment or legal recourse when Amgen, Inc., the biotech firm that holds the patent for GDNF, suddenly withdrew the drug from testing amidst allegations of safety and efficacy concerns.
Amgen's own bioethicist told CBS that the decision was largely a result of a nervous pharmaceutical industry haunted by the specter of the Vioxx lawsuits. CBS also uncovered video footage in which an Amgen executive stated that the treatment in its current incarnation, a complex procedure involving deep brain surgery, would not be a money maker for the corporation. Shortly after halting the trial and withdrawing all GDNF treatment from patients, Amgen applied for a new patent on a different form of GDNF that could potentially be delivered in a more economical capsule form.
Despite the requests of investigators, the pleas of patients and the approval of the Food and Drug Administration, Amgen has refused to provide the drug under compassionate use guidelines to those patients who had undergone surgery to implant a pump and catheter in their brains, and had been receiving GDNF successfully for as long as two years. Court cases in Kentucky and New York have been dismissed and appeals are being considered.
While distinctly troubled by the plight of patients caught in the crossfire of the first GDNF trials, Gerhardt says Parkinson's researchers are far from giving up all hope in GDNF. He continues to work with the drug in animal models, and to explore similar molecules to which Amgen does not possess patent rights. By exploring multiple paths of research at once, Gerhardt and his colleagues are applying the old maxim "don't put all your eggs in one basket," to the newest science imaginable.
"History is riddled with examples of technology that failed more than once before being perfected. The Wright brothers crashed a few airplanes. GDNF has not failed so spectacularly, although we still have much to learn about it. We're going to spend the next five years studying the technology and how to translate it into clinical use in patients," said Gerhardt.
The GDNF trial launched at UK in 2002, and was headed by principal investigator John Slevin, M.D., professor in the UK Department of Neurology and Department of Pharmacology and director of the Movement Disorders Clinic at UK; Gerhardt; Don Gash, Ph.D., the UK Alumni Chair in Anatomy and Neurobiology, professor in the Department of Anatomy and Neurobiology, and director of the M. Margrite Davis-Ralph E. Mills Magnetic Resonance Imaging and Spectroscopy Center at UK; Byron Young, M.D., the Johnston-Wright Endowed Chair of Surgery, professor, Department of Surgery, and chief, Division of Neurosurgery, associate dean for Clinical Affairs, and chief of staff, UK Hospital. Ten patients participated in the trial through UK, joining approximately 40 others in the United States and the United Kingdom.