Table 1.

NHP trials and clinical trials utilizing AADC

Author	Method	Subjects	Results	Reference
Bankiewicz et al. (2000)	Bilateral convection enhanced delivery AAV induced AADC expression in nu. caudatus, putamen and globus pallidus.	MPTP-treated rhesus monkeys (n = 4).	Higher increase in gene expression using CED than conventional injection. Strong AADC expression in striatum.	[33]
Daadi et al. (2006)	Bilateral convection enhanced delivery AAV induced AADC expression in nu. caudatus, putamen and globus pallidus.	MPTP-treated macaque monkeys (n = 4).	Verification of strong striatal AADC expression after 3 years.	[32]
Forsayeth et al. (2006)	Dose ranging study with bilateral putaminal injection of AAV2-AADC in escalating doses.	MPTP-treated macaque monkeys (n = 12).	A minimum dose is needed to increase L-DOPA response and FMT-activity in striatum.	[31]
Bankiewicz et al. (2006)	Unilateral AAV-2 induced AADC expression in striatum.	MPTP-lesioned macaque monkeys (n = 8).	PET-verified increase in AADC activity after 2 years. Consistently higher L-DOPA sensitivity in treatment group.	[30]
Eberling et al. (2008)	Open label study. Bilateral AAV2-induced AADC expression in putamen.	Severely affected PD patients (n = 5).	Modest improvement of OFF-state UPDRS-score. 30% increase in putaminal FMT activity at 6-month follow-up.	[14]
Christine et al. (2009)	Open label study. Bilateral AAV2-induced AADC expression in putamen. High and low dosage.	Moderately affected PD patients (n = 10).	Improvement of UPDRS scores. Longer time in ON-state. Therapy well tolerated. High dose with higher FMT-activity than low dose at 6-month follow-up.	[12]
Hadaczek et al. (2010)	8-year follow up on the study by Bankiewicz et al. (2006).	MPTP-lesioned macaque monkeys (n = 2).	No decrease in FMT signal and continued robust AADC expression.	[183]
Muramatsu et al. (2010)	Open label study. Bilateral AAV2-induced AADC expression in putamen.	Moderately to severe affected PD patients (n = 6).	Decrease in UPDRS scores by 46% in OFF-state. At 6-month follow-up. Persistent FMT activity at 24 weeks.	[25]
Mittermeyer et al. (2012)	4-year follow-up on Christine et al. (2009).	Moderately affected PD patients.	Discrete decline in AADC activity at 4-year follow-up. Slight increase in UPDRS-score.	[24]

Clinical and preclinical studies with AADC-gene therapy. FMT, ¹⁸Fluoro-L-m-tyrosine, a tracer specific for AADC.