Gene Therapy - Parkinsonism

GENE THERAPY

Three phase 1 (safety) trials of gene therapy for Parkinson’s disease have now been completed in the USA. All trials involved infusion into the striatum of adeno-associated virus type 2 as the vector for the gene. The genes were for glutamic acid decarboxylase (GAD, to facilitate synthesis of GABA, an inhibitory neurotransmitter), infused into the subthalamic nucleus to cause inhibition; for aro-matic acid decarboxylase (AADC), infused into the putamen to increase metabolism of levodopa to dopamine; and for neurturin (a growth factor that may enhance the survival of dopaminergic neurons), infused into the putamen. All agents were deemed safe and the data suggested efficacy. A phase 2 study of the GAD gene has been completed and the results are encouraging. A similar study of AADC is planned but has not yet started. A phase 2 study of neurturin failed to show significant benefit, but a new phase 2 study has been initiated in which neurturin is infused into the substantia nigra as well as the putamen.

THERAPY FOR NONMOTOR MANIFESTATIONS

Persons with cognitive decline may respond to rivastigmine (1.5–6 mg twice daily), memantine (5–10 mg daily), or donepezil (5–10 mg daily) ; affective disorders to antide-pressants or anxiolytic agents ; excessive daytime sleepiness to modafinil (100–400 mg in the morning) ; and bladder and bowel disorders to appropriate symp-tomatic therapy .