The Michael J Fox Foundation for Parkinson's Research (MJFF) has awarded a grant to the team, led by Olle Lindvall of the University of Lund, to develop a neuroprotective therapy based on the implantation of encapsulated cells that produce the growth factor glial-derived neurotrophic factor (GDNF) directly into the brain.
Prior research has suggested that GDNF could have a protective influence on the dopamine neurons that typically degenerate in Parkinson's disease. But because the protein is too big to cross the blood-brain barrier - a membrane designed to protect the brain from toxic damage - it cannot be given orally or by injection.
The encapsulated cell technology could, if successful, enable localised, long-term sustained delivery of GDNF to the brain with the primary aim of protecting dopamine neurons and stimulating their regeneration, potentially slowing, halting or even reversing the degenerative effects of Parkinson's disease, said Deborah Brooks, executive director of the Foundation.
Prior studies of GDNF in Parkinson's disease have shown positive effects in animal models as well as in early clinical trials. However, the results of a Phase II trial carried out by Amgen, employing a pump-based delivery system for GDNF, showed no clinical improvement after six months.
Indeed, Amgen had been exploring the use of GDNF in Parkinson's in the late 1990s, but dropped it from development after initial studies were disappointing. The project was only re-established after a separate research group showed that continuous infusion of the drug into the area of the brain affected by Parkinson's disease using an implantable pump seemed to provide some benefit.
The MJFF said that Amgen's study did not look at the ability of GDNF to protect dopamine neurons and stop the progression of the disease, and that it is this factor that will be addressed in the Lund project.
Full funding for the project is contingent upon the achievement of predetermined scientific milestones. The team's first milestone will be to generate human cell lines capable of steadily secreting small amounts of GDNF and place these cells in retrievable fibre capsules.
Once created, these capsules will be tested to assess cell viability, level and duration of GDNF secretion and diffusion into the brain, along with general safety issues such as inflammation and retrievability.
In addition, the neuroprotective and regenerative effect of this type of delivery of GDNF will be studied in disease models. Should this therapy prove effective, 12 patients will be enrolled in clinical trials in Sweden, Switzerland, Germany and the UK and will be assessed clinically for at least 24 months.