Results of Gene Therapy in Parkinson Disease Support Further Study
Positive results from another phase 1 study* of gene therapy in Parkinson disease (PD) support continued investigation of the novel treatment method. Details of the Avigen- and Genzyme-supported trial are available in an advanced, online edition of Neurology.
Ten patients (5 men, 5 women) with intractable motor fluctuations, despite optimal medical treatment of PD, received bilateral putaminal infusions (1 of 2 doses) of the human gene for aromatic L-amino acid decarboxylase (AADC) in an adenovirus vector. (A progressive deficiency of AADC, which converts levodopa into dopamine, may cause the diminishing response to L-dopa therapy that is observed in idiopathic PD.) Both doses were associated with improved mean motor function at 6 months, objectively (~30%) and subjectively, with a reduction of troublesome dyskinesias. Clinical improvement was also associated with a nonsignificant reduction in the level of dopaminergic medications. PET images demonstrated AADC activity in the putamen, thereby mitigating a possible placebo effect; tracer uptake was higher with high-dose gene therapy.
Three patients experienced intracranial hemorrhage, 1 symptomatic and 2 asymptomatic, which appeared to be due to placement of the gene-delivering catheters.
The authors propose similar follow-up studies with the high-dose therapy and a placebo group.
PET = positron emission tomography.
* The 2 previous studies, which used different genes: Kaplitt MG et al. Lancet. 2007;369:2097-2105; Marks WJ et al. Lancet Neurol. 2008;7:400-408.
Image of 1886 drawing of PD patient by neurologist Sir William Richard Gowers at Wikimedia Commons.
