%0 Journal Article
%T Critical Aspects of Clinical Trial Design for Novel Cell and Gene Therapies
%A Zinovia Kefalopoulou
%A Iciar Aviles-Olmos
%A Thomas Foltynie
%J Parkinson's Disease
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/804041
%X Neural cell transplantation and gene therapy have attracted considerable interest as promising therapeutic alternatives for patients with Parkinson's disease (PD). Preclinical and open-label studies have suggested that grafted fetal neural tissue or viral vector gene transfer can achieve considerable biochemical and clinical improvements, whereas subsequent double-blind, placebo-controlled protocols have produced rather more modest and variable results. Detailed evaluation of these discordant findings has highlighted several crucial issues such as patient selection criteria, details surrounding transplantation or gene therapy methodologies, as well as the study designs themselves that ought to be carefully considered in the planning phases of future clinical trials. Beyond the provision of symptomatic efficacy and safety data, it also remains to be identified whether the possibilities offered by stem cell and gene therapy technological advances might translate to meaningful neuroprotection and/or disease-modifying effects or alleviate the nonmotor aspects of PD and thus offer additional benefits beyond those achieved through conventional pharmacotherapy or deep brain stimulation (DBS). 1. Introduction Current antiparkinsonian oral drug therapies, with the dopamine (DA) precursor levodopa (L-dopa) remaining the most effective, allow remarkable symptomatic control over the cardinal motor features of Parkinson¡¯s disease (PD) in the first years after diagnosis, by restoring the characteristic nigrostriatal DA deficit. Unfortunately, the pharmacotherapeutic window shrinks over time, and treatment is complicated by the onset of motor fluctuations (¡°ON/OFF¡± phenomena) and L-dopa induced dyskinesias (LIDs), while signs such as balance disorders, gait freezing, autonomic disturbances, dementia, or affective changes, refractory to dopaminergic substitution, appear [1¨C3]. Continuous delivery of the DA agonist apomorphine (subcutaneously) or L-dopa (intraduodenally) and surgical strategies such as deep brain stimulation (DBS) provide relief in advanced PD patients with severe motor complications [4¨C6]. These therapeutic advances, nevertheless, do not influence the underlying neurodegenerative process and have limited effects on L-dopa nonresponsive clinical manifestations, which are now clearly recognized as causes of major disability in late-stage PD [3, 7, 8]. Hence, there is a pressing demand for innovative approaches. Cell replacement therapies and gene transfer through viral vectors into the degenerated host brain have been investigated as alternatives to
%U http://www.hindawi.com/journals/pd/2011/804041/