title: Repairing the Aged Parkinsonian Striatum: Lessons from the Lab and Clinic.
abstract: The primary risk factor associated with Parkinson's disease (PD) is advanced age. While there are symptomatic therapies for PD, efficacy of these eventually wane and/or side-effects develop over time. An alternative experimental therapy that has received a great deal of attention over the past several decades has been neural transplantation aimed at replacing nigral dopamine (DA) neurons that degenerate in PD. However, in PD patients and parkinsonian rats, advanced age is associated with inferior benefit following intrastriatal grafting of embryonic DA neurons. Traditionally it has been thought that decreased therapeutic benefit results from the decreased survival of grafted DA neurons and the accompanying poor reinnervation observed in the aged host. However, recent clinical and preclinical data suggest that factors inherent to the aged striatumper selimit successful brain repair. In this short communication, we focus discussion on the implications of our recent grafting study in aged parkinsonian rats, with additional emphasis on a recent clinical report of the outcome of cell therapy in an aged PD patient with long-term (24 years) survival of DA neuron grafts. To address aging as a limiting factor in successful brain repair, we use the example of cell transplantation as a means to interrogate the environment of the aged striatum and identify factors that may, or may not, respond to interventions aimed at improving the prospects for adequate repair of the aged brain. We offer discussion of how these recent reports, in the context of other historical grafting studies, might provide new insight into specific risk factors that have potential to negatively impact all DA cell or terminal replacement strategies for clinical use in PD.
authors.affiliation: Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
authors.forename: Natosha M
authors.initials: NM
authors.lastname: Mercado
authors.affiliation: Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary's, Grand Rapids, Michigan 49503, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Collier
authors.affiliation: Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, College of Medicine, University of South Florida, FL 33612, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Freeman
authors.affiliation: Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary's, Grand Rapids, Michigan 49503, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Steece-Collier