Ultrasound-based gene therapy restores neuron function in PD rats

Researchers at the University of Virginia have developed a novel, non-invasive approach to deliver therapeutic gene and restore dopaminergic neuron function in a rat model of Parkinson’s disease (PD). The approach used a combination of magnetic resonance (MR) image-guided focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN).

Gene therapy to deliver neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF) are currently being tested in clinical trials for the treatment of PD. However, there have been a number of obstacles found associated with this approach, including the poor distribution of vectors throughout the affected brain regions, and the necessity of invasive procedures which eliminate inclusion of early-stage patients as trial candidates, despite the approach affording them the most potential benefit.

In the present study published in Nano Letters, Dr Richard Price and team developed a combinatorial approach to overcome the limitations of current gene delivery strategies, thereby providing a novel strategy to treat PD. Originally developed at the same university in 2014, this FUS and BPN combinatorial approach was designed to tackle these two issues by using a non-invasive route to deliver nanoparticles.

In the procedure, GDNF-carrying BPNs were administered intravenously to a rat model of PD. MR image-guided FUS was then used to allow circulating gene vectors to travel into the brain tissue by non-invasive and transient opening of the blood-brain barrier (BBB) within the areas where FUS was applied. Once the vectors crossed BBB, BPN distributed GDNF uniformly in the targeted rat brain tissue.

Results demonstrated therapeutically significant levels of GDNF protein expression in the FUS-targeted regions in PD rats following a single treatment and this effect lasted at minimum up to 10 weeks. Furthermore, dopamine levels and dopaminergic neuron density were restored along with reversed behavioral indicators of PD-associated motor dysfunction. No evidence of local or systemic toxicity was found associated with the approach.

Findings from the study provide a promising new approach for overcoming the challenges associated with developing gene therapies to treat PD.

Source: Novel focused ultrasound gene therapy approach non-invasively restores dopaminergic neuron function in a rat Parkinson’s disease model. Mead BP et al., Nano Letters May 2017. DOI