First clinical trials: Neural grafts in Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative condition of unknown aetiology, for which there is a treatment but no cure. As discussed in the Chapter Four the core pathology in PD is the loss of the dopaminergic nigrostriatal pathway, and thus the mainstay of current therapy is in pharmacologically restoring this network. The main drugs that are commonly used in PD are l -dopa, which is converted into dopamine by the remaining dopaminergic neurones of the nigrostriatal tract, and dopamine agonists (e.g. bromocriptine, pergolide, lisuride, apomorphine, and ropinirole), which directly activate dopamine receptors within the CNS (central nervous system). These agents are effective early on in the disease but, with time, complications of therapy start to appear and these initially consist of wearing off phenomena and unpredictable changes in the patient’s motor state from one of relative normality (“on”) to one of relative immobility (“off”). Furthermore, the drugs induce a range of unwanted movements, “dyskinesias”, which the patient can find especially disabling. As a result, 5–10 years after first developing symptoms, patients with PD often have major problems in the control of their disease despite taking complex regimes of medication (reviewed in Stocchi et al., 1997 ).