Objective/Rationale:
GDNF has the potential to halt the progression of, or reverse, PD. However, GDNF, a large protein, does not get into the brain when given orally or intravenously. Our novel nano-sized vesicles, called V-SmartTM, encapsulate proteins, cross the blood-brain barrier and release their drug contents in the brain. We intend to customize V-SmartTM vesicles for the delivery of GDNF to the brain to protect and restore nerve cells that deteriorate during the course of PD.
Project Description:
Our V-SmartTM nano-vesicles, when administered intravenously, can cross the blood-brain barrier (BBB) and release their contents (large proteins, peptides or small molecules) within the brain, without toxicity. We will optimize V-SmartTM vesicles for GDNF delivery to brain regions affected in PD, by synthesizing new components that improve the vesicles’ brain penetration and achieve targeted binding to the nerve cells (dopaminergic neurons) that degenerate during the course of PD. V-SmartTM vesicles showing the highest GDNF load, stability and brain penetrability will be administered intravenously to pre-clinical models to determine encapsulated and released GDNF tissue distribution. We will then choose formulations and dosages that produce maximum GDNF delivery to brain nerve cells most affected by PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Successful delivery to the brain of our optimized V-SmartTM vesicles, formulated with GDNF, will enable us to perform future efficacy studies in PD pre-clinical models and, thereafter, clinical studies for PD patients. The project’s potential is that V-SmartTM vesicles, loaded with GDNF and delivered to degenerating dopaminergic neurons in the brain, can become a PD treatment to stop progression of, and possibly reverse, PD, unlike other drugs that provide merely Symptoms & Side Effects relief.
Anticipated Outcome:
We expect to learn how to customize the V-SmartTM nanovesicles to contain large amounts of GDNF and deliver them non-invasively to brain nerve cells affected in PD. We further expect to demonstrate that V-SmartTM vesicles arrive intact to the brain, bind
to the dopaminergic neurons that deteriorate in PD and release in the brain a beneficial concentration of GDNF, so we can affect the course of PD.
Final Outcome
Lauren Sciences has demonstrated successful delivery of GDNF to the brain by our optimized V-SmartTM nanovesicles for the purpose of protecting and restoring nerve cells that deteriorate during the course of PD. We optimized V-SmartTM vesicles for GDNF delivery to brain regions affected in PD by designing and synthesizing new components to improve the vesicles’ brain penetration and to target the vesicles to the brain nerve cells (dopaminergic neurons) that degenerate during the course of PD. The optimized V-SmartTM nanovesicles were shown to penetrate into the brain following intravenous injection in pre-clinical models, and, within the brain, to target to the areas of the degenerating nerve cells. Furthermore, we have demonstrated that these GDNF-loaded V-SmartTM nanovesicles release GDNF, so we can potentially stop progression of, and possibly reverse, PD. This successful outcome of our project will enable us to conduct efficacy studies in pre-clinical PD models and then, if successful, proceed with clinical studies in PD patients. Our ultimate goal is to have on the market a V-SmartTM therapeutic for PD.