Critical Aspects of Clinical Trial Design for Novel Cell and Gene Therapies

Table 2

Patient-centred comparison of gene therapy interventions for PD.

Gene therapy strategy	Advantages	Disadvantages	Patient target group
Neurotrophic factor delivery	Disease-modifying/neuroprotective potential	Likely to cause structural and functional effects beyond the intended targets	Early-stage PD
Prodrug approach	(i) Striatal DA synthesis dependent on subsequent peripheral administration of L-dopa → modulation of; (ii) Therapeutic effect still within control of the clinician	(i) Possibility of accumulation of DA in striatal neurons; (ii) Increased endogenous DA production, without increased vesicular dopamine storage, could potentially exacerbate dyskinesia	(i) More advanced-stage PD with motor complications; (ii) Patients with inadequate striatal AADC activity
Ectopic DA production	(i) Independent of peripheral L-dopa; (ii) Independent of endogenous AADC activity		(i) More advanced-stage PD with motor complications; (ii) Patients with inadequate striatal AADC activity
Continuous DOPA delivery strategy	(i) Site specific continuous DA—supply; (ii) Independent of peripheral L-dopa	Depends on sufficient endogenous AADC activity	(i) More advanced-stage PD with motor complications; (ii) Patients with sufficient striatal AADC activity
Modulation of basal ganglia activity	Proposed to mimic clinical results of DBS, which has established clinical effectiveness	(i) Limited experience; (ii) Safety concerns due to bilateral irreversible nature of the technique	Same as DBS