Huiliang Wang

Investigator:

Huiliang Wang, PhD

Name of Institution:

University of Texas at Austin, Austin, TX

Project Title:

Sono-optogenetic stimulation for Parkinson disease treatment in rats


Investigator Bio:

Dr. Wang is an Assistant Professor in the biomedical engineering department at University of Texas at Austin, where he leads his research team in the design of functional nanomaterials, electronic devices, and genetic technology in neural interface engineering. In particular, his lab focuses on the development of new tools to modulate and record neural activity from targeted neuronal populations using minimally invasive methods. During his doctoral dissertation under the supervision of Prof Zhenan Bao at Stanford University in California, he developed nanomaterials and polymers for flexible and wearable applications. His postdoctoral research with Prof Karl Deisseroth in the Stanford University Bioengineering department focused on the development of nanomaterial-based technologies for targeted, minimally invasive neural modulation. He obtained both an NIH F32 Postdoctoral Fellowship and an NIH K01 Mentored Research Scientist Development Award during his postdoctoral research.

Objective:

The objective of this proposal is to apply the technology of sono-optogenetics in rats to achieve long-lasting motor recovery in a rat model of Parkinson’s disease (PD).

Background:

A significant limitation of the existing deep brain stimulation (DBS) therapy for PD is that it treats symptoms of the disease in the short-term, but does not correct the underlying circuit dysfunction responsible for PD symptoms. As a result, symptoms rapidly return once DBS stimulation is turned off. Achieving the next level in long-term therapeutic efficacy of DBS will require the development of strategies to repair circuit dysfunction through targeted neuromodulation technology. In addition, DBS currently requires invasive steps such as the formation of a hole in the skull and the implantation of an electrode in brain tissue.

Methods/Design:

Optogenetics is a technique that uses light to control cellular processes. Neurons can be genetically modified so that they express light-sensitive ion channels. The neurons are then exposed to light in specific spatial or temporal patterns to allow for manipulation of these ion channels, and therefore manipulation of electrical circuitry in the brain.

In this work, we will apply a modified optogenetics technology in a rat model of PD called sono-optogenetics. We will use nanoparticles (tiny particles that are between 1 and 500 nanometers in diameter) that can circulate in the blood stream, and only emit light when they are stimulated by focused ultrasound. The light will then be used to control the certain neuron types that contain the light sensitive ion channels.

Using this system, we aim to control brain circuitry in a spatial and temporal manner. We will study whether this system achieves longer-lasting motor recovery than achieved using deep brain stimulation without the need for electrode implantation. We will assess various rat motor tasks to examine the therapeutic efficacy of sono-optogenetic stimulation.

Relevance to Diagnosis/Treatment of Parkinson’s disease:

This proposed work is expected to be the first step towards the clinical translation of sono-optogenetics as a better treatment method (non-invasive, long-lasting effect) for Parkinson’s disease as compared to current DBS approaches