Cell Therapy for Parkinson’s Disease: Failure or Success?

Abstract

The mature central nervous system (CNS) is probably the most complex structure known in nature. This fact and the irreversibility of most forms of clinical brain damage are the basis for the long-held belief that the adult brain cannot restore itself and cannot be repaired. Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) with a concomitant loss of the catecholamine called dopamine (DA), the neurotransmitter released at the axon terminals of the SNPc neurons that project to the striatum (caudate nucleus and putamen) (Fig.1). Historically, the therapy for PD is aimed at reinstalling proper stimulation of the dopamine receptors in striatum. The dramatic breakthrough was the introduction of L-DOPA treatment in 1969 (Cotzias et al., 1969). L-DOPA, the precursor of dopamine, passes the blood-brain barrier (BBB) and is converted to dopamine, which becomes available for dopamine receptors in striatum, thereby improving the balance between excitatory and inhibitory influences in this brain region. Together with L-DOPA treatment, dopamine reuptake inhibitor, dopaminergic agonists and muscarinic antagonists also have a clinical effect. Despite this pharmacologic advance in treatment, there remains no cure for PD. Because PD is a neurodegenerative process and long term therapy is necessary, development of severe side effects such as dyskinesias (movement disorder), limits the usefulness of L-DOPA therapy over time and progressively becomes less effective; consequently, patients become more troubled by freezing or akinesias. In addition, L-DOPA will not only reach the striatum, but the entire CNS as well as the rest of the body, where it can develop unwanted side effects. Additionally, surgical treatment is being used to treat people with advanced PD for whom drug therapy is no longer sufficient. The more frequently employed techniques are thalamotomy, lesion of the internal globus pallidus or subthalamic nucleus and chronic implantation of electrodes for deep brain stimulation, amongst others. Even though there is a clinical recovery in PD patients after surgical therapy, as seen with pharmacological therapy, the progression of the disease cannot be avoided. Hence, the basic principle of