Evaluation of a Viral Non-coding RNA as a Neuroprotective and Neurorestorative Therapy in Chronic Models of Parkinson's Disease
Rapid Response Innovation Awards, 2009
This grant builds upon the research from a prior grant:
Promising Outcomes of Original Grant:
Previously, we asked whether a novel viral non-coding RNA (an RNA which does not appear to encode a protein), but with known pro-life functions, could act to protect neurons in experimental models of Parkinson’s disease (PD) which involved direct lesion of the substantia nigra (SN). Our results to date have shown unequivocally that this viral non-coding RNA is neuroprotective when it is delivered directly to the SN by injection as well as when it is delivered by injection into the bloodstream. In both cases, the viral RNA inhibits neuronal cell death in the SN.
Objectives for Supplemental Investigation:
Such direct experimental lesion of the SN results in rapid and acute loss of dopaminergic neurons which is generally not the case in patients with PD. In contrast, 6-OHDA lesion of the striatum (a so-called striatal lesion) results in a more gradual loss of dopaminergic neurons in the SN and can be used as a model to study strategies which might rescue the nigrostriatal pathway as it is damaged over a longer period of time – so-called chronic damage.
We will address important questions to determine if the novel non-coding viral RNA can also act effectively in chronic models of neuron loss, how long the RNA can stay in the brain and whether it can also act to restore neuronal function if delivered after the experimental lesion.
Importance of This Research for the Development of a New PD Therapy:
The novel therapeutic RNA we have already identified clearly protects neurons in the SN from cell death when we deliver the RNA prior to a rapid and direct experimental lesion of the SN. If this RNA can also protect neurons in chronic models of PD (using a striatal lesion model of PD) and if it can also be delivered after the lesion and still restore neuron function, this novel non-coding viral RNA would fulfill many of the requirements for a novel therapeutic to prevent neuronal death associated with Parkinson’s disease.
Professor of Molecular Virology in the Department of Medicine at University of Cambridge
Location: Cambridge, United Kingdom