This article was written in Nov 2013 for my course.
Abstract
Parkinson’s disease (PD) has been considered as a disease leading to debilitating motor symptoms due to the progressive focal death of dopaminergic neurons in the substantia nigra (SN). Different therapeutic strategies aiming to restore this dopaminergic network with transplantation of a variety of cells have yielded promising results both in the lab and the clinic and offered a definite proof of principle. Yet, even though clinical trials have shown that restoration of dopamine is feasible, have many times failed to produce significant and meaningful benefits and, moreover, they are often complicated by variability and the development of new abnormal motor symptoms. This has not only led to a very fertile discussion about the issues that need to be overcome but also to the realisation that new perspectives are needed towards both cell replacement therapies and PD. Understanding that cell transplantation creates novel conditions not found in the premorbid or morbid brain, while appreciating the widespread effects of PD which cannot be reduced in the focal loss of dopaminergic cells, maybe perhaps the only way to overcome the inherent obstacles posed to cell replacement therapies in PD and to further develop novel therapeutic strategies.
Introduction
Parkinson’s Disease (PD) is classically considered as a progressive, neurodegenerative disease that manifests itself clinically with the cardinal triad of tremor, bradykinesia (difficulty in initiating and executing muscle movement) and rigidity, as a result of extensive loss of dopaminergic neurons (60-80%)[1, 2] located in a part of the midbrain called substantia nigra pars compacta (SNc). SNc neurons innervate the putamen of the striatum and both are part of a complex neural circuit involved in modulating movement (see figure 1 and [3,4]). However, PD’s pathophysiology is multifactorial and not well understood[5; for a brief review] and even if the involvement of other parts of the brain producing motor and non-motor symptoms is recognised (see later), most current therapeutic approaches aim principally in the restoration of the dopamine levels (e.g. administration of levodopa) and amelioration of the related symptoms. Nonetheless, the presumed neuropathological specificity of PD: the focal loss of a single cell type innervating a particular structure, made it an excellent candidate for cell replacement therapy (CRT) with the ultimate view of replacing neuronal losses and restoring neuronal circuitry to the premorbid status.[6]
