How far is RNAi from the neurology clinic?

With all this talk about RNAi, where do we stand currently? There is potential to treat several diseases with RNAi but how far have we progressed? For conditions like age-related macular degeneration, respiratory syncytial virus and hepatitis C infection, several human phase and II therapeutic RNAi trials have already been completed or are nearing completion. However, none of these early trials have targeted a brain disease.
So what is so different when it comes to these neurodegenerative disorders? Perhaps the biggest challenge facing the field of RNAi research is achieving safe and efficient delivery of therapeutic RNAi agents to neurons—highly specialized, postmitotic cells protected by the blood-brain barrier. The chronic nature of many brain disorders also means that sustained delivery of an RNAi reagent, or its repeated administration, will be required to achieve a long-term benefit. Furthermore these diseases are not attributable to single genetic defect which makes RNAi therapy difficult.

But even before we think of carrying out human trails the chosen strategy will need to undergo preclinical testing in validated animal models. The first successful RNAi trial for a neurodegenerative disease was completed in a transgenic mouse model of Spinocerebellar ataxia (SCA) type1. SCA1 is a dominantly inherited polyglutamine expansion disorder, the mutant ataxin-1 protein acts via a toxic, gain-of-function mechanism that causes neuronal dysfunction and cell death in the cerebellum and certain brainstem nuclei. Mice lacking the Atxn1 gene show only subtle behavioral abnormalities, suggesting that RNAi-mediated knockdown of both alleles in humans would be unlikely to result in adverse effects caused by loss of gene function.
Since the first report of successful therapeutic RNAi in SCA1 mice, many successful preclinical trials in mouse models of other neurodegenerative diseases such as familial ALS (SOD1), familial PD (α-synuclein), and HD (huntingtin) have been completed and have had their results published. These trials have used different RNAi effector molecules, explored various delivery methods (mostly virus-mediated delivery), and targeted diverse anatomical areas ranging from the hippocampus to motor neurons and muscle.
While initial studies in cellular and animal models of neurodegenerative disease have produced encouraging results, the safety of this therapy in the diseased human CNS has not, however, been established. Whether RNAi therapy is an effective way to treat incurable neurodegenerative diseases?!...only the future can tell! As of now all we can say is that there is potential.
The following article discusses how far RNAi therapy is from the neurology clinic:
http://www.medscape.com/viewarticle/559503