This grant builds upon the research from a prior grant: Utilization of Aptamers to Prevent Protein Aggregation in Parkinson’s Disease
Promising Outcomes of Original Grant:
Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). In our first project funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF), we discovered a new type of molecule, aptamer, which can bind to alpha-synuclein and prevent it from clumping. Aptamers are short strands of the cell's genetic material, DNA, folded in 3D shapes that can bind to other molecules (e.g., alpha-synuclein). Of several aptamers discovered, one in particular, a-syn-1, effectively prevented alpha-synuclein aggregation in cellular experiments and pre-clinical models.
Objectives for Supplemental Investigation:
In the present project, we aim to better understand where aptamer travels once it is injected into a pre-clinical model. Specifically, we will inject aptamer into the stomach of a pre-clinical model and evaluate the amount of aptamer in the brain, blood and liver. We will inject two different doses to understand whether higher amounts allow more aptamer to reach the brain and help combat alpha-synuclein clumping. Finally, we will study how aptamer is distributed in the body over a period of time. These studies may help deepen our understanding of whether aptamer can prevent clumping of alpha-synuclein in the brains of people with PD and stop disease progression.
Importance of This Research for the Development of a New PD Therapy:
Once we understand how aptamer behaves in the body, we will be ready to inject it into pre-clinical models with Parkinson's symptoms to determine its ability to slow or stop damage to brain cells. This work aims to validate aptamer as a therapeutic target for treating Parkinson's.
Promising Outcomes of Original Grant:
Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). In our first project funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF), we discovered a new type of molecule, aptamer, which can bind to alpha-synuclein and prevent it from clumping. Aptamers are short strands of the cell's genetic material, DNA, folded in 3D shapes that can bind to other molecules (e.g., alpha-synuclein). Of several aptamers discovered, one in particular, a-syn-1, effectively prevented alpha-synuclein aggregation in cellular experiments and pre-clinical models.
Objectives for Supplemental Investigation:
In the present project, we aim to better understand where aptamer travels once it is injected into a pre-clinical model. Specifically, we will inject aptamer into the stomach of a pre-clinical model and evaluate the amount of aptamer in the brain, blood and liver. We will inject two different doses to understand whether higher amounts allow more aptamer to reach the brain and help combat alpha-synuclein clumping. Finally, we will study how aptamer is distributed in the body over a period of time. These studies may help deepen our understanding of whether aptamer can prevent clumping of alpha-synuclein in the brains of people with PD and stop disease progression.
Importance of This Research for the Development of a New PD Therapy:
Once we understand how aptamer behaves in the body, we will be ready to inject it into pre-clinical models with Parkinson's symptoms to determine its ability to slow or stop damage to brain cells. This work aims to validate aptamer as a therapeutic target for treating Parkinson's.