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Assessing a Novel Strategy for Noninvasive Stimulation of Dopamine-producing Neurons in Preclinical Models of Parkinson’s Disease

Rationale: Parkinson’s disease (PD) is caused by the progressive degeneration of the dopamine-producing neurons responsible for initiating and refining voluntary movements. Treatments based on drugs that replace dopamine ameliorate PD’s motor symptoms, but their action wanes with time and is often accompanied by long-term side effects, such as dyskinesias. When individuals in the advanced stages of PD stages become resistant to these drugs, the only alternative is invasive Deep Brain Stimulation. Novel therapeutic strategies that mimic the action of dopamine are therefore in high demand to ensure long-term efficacy combined with minimal invasiveness. 

Hypothesis: We will develop an innovative therapeutic platform that uses infrared light to stimulate neurons inactivated by the loss of dopamine. We hypothesize that this noninvasive approach can be used to rescue PD symptoms in an experimental model of PD.  

Design: In this study, we will develop hybrid nanotools that can be administered intravenously to target the neurons that are inactivated by the loss of dopamine in PD. These nanotools also contain photoactive particles that can convert light into electrical signals. Once they reach their target, these particles can be remotely activated by infrared light to electrically stimulate the target neurons. We will determine whether these nanotools can cross the blood-brain barrier and excite the selected neuronal population. Finally, we will assess whether this approach can rescue motor deficits in a well-known preclinical model that reproduces the clinical symptoms of PD. 

Impact on Treatment of Parkinson’s disease: This approach could provide an effective, cell-specific strategy to activate neurons in areas of the brain that are difficult to access. By mimicking the physiological activation of neural circuits, it should be possible to alleviate symptoms in drug-resistant forms of PD in a totally noninvasive fashion.

Next Steps: If successful, this innovative therapeutic opportunity can be validated in preclinical, nonhuman primate models of PD before the first-in-man application. 


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