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Funded Studies

Optogenetic Restoration of Basal Ganglia Function to Treat Parkinson’s Disease

Study Rationale:                   
Optogenetics has gained wide interest as a tool to understand the function of circuits influencing brain diseases. This approach uses proteins that respond to particular wavelengths of light. Using gene therapy techniques, these proteins can be produced to either activate or inactivate when exposed to particular types of light. If this can be developed for human use, it holds great potential for normalization of brain function in Parkinson’s disease (PD).

We hypothesize that gene therapy to deliver light-sensitive proteins into specific brain cells, followed by activation or inactivation with light delivered from an implanted probe, can normalize the function of the basal ganglia circuit controlling movement and improve symptoms in models of PD.

Study Design:
We will first deliver genes for light-sensitive proteins to brain regions that are dysfunctional in PD, followed by light probes to normalize neuronal functions. This will first be tested in a pre-clinical PD model in which symptoms develop after dopamine cells are chemically destroyed.

A second model will use optogenetics to activate neurons normally blocked by dopamine, which mimics the loss of dopamine and creates typical PD symptoms. We can use this to test our treatment in models with mild to severe forms of PD.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
The precision of optogenetics holds the potential for improved normalization of circuits that are dysfunctional in PD, while the use of light rather than electricity (such as in deep brain stimulation) may reduce the risk of adverse effects caused by non-specific influences on unintended targets.

Next Steps for Development:
Successful completion of this study will generate sufficient data to determine the feasibility of optogenetics as a potential treatment for PD patients, which would justify development of tools for human use and testing in larger models.

Final Outcome

During the course of this year, our major goal was to identify whether one or more of the available optogenetic tools could be effective at reversing the movement abnormalities in parkinsonian pre-clinical models.  We have now tested several known “opsins”, and have found that some of the newest genes did not function as we had hoped.  However, we found that at least two other known agents were extremely effective at reversing many abnormalities in pre-clinical models with experimental parkinsonism.  We found that abnormal electrical firing of the subthalamic nucleus (STN), a primary target of DBS in current clinical practice, was reversed by light of various intensities following introduction of two of the known “opsin” genes into STN neurons.  In freely moving animals, this same approach led to substantial improvements in abnormal spontaneous rotating behaviors, and improved overall levels of activity in an open cage environment as well as increased the use of the affected paw compared with animals receiving genes which did not render cells responsive to light.  Our data provides important support for potential further development of this new technology as a potential novel therapy which combines the advantages of DBS and gene therapy.


  • Michael Gordon Kaplitt, MD, PhD

    New York, NY United States

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