Effect of Dietary Ketosis On Alpha-Synuclein Accumulation
Rapid Response Innovation Awards, 2014
A key feature of Parkinsonís disease is abnormal accumulation of the protein alpha-synuclein. Production of organic compounds called ketones is a normal metabolic process that occurs when glucose availability is low, such as during calorie restriction and in low-carbohydrate diets. Ketones stimulate the breakdown of proteins in the liver. Therefore, it is possible that ketone production could help to reduce abnormal accumulation of alpha-synuclein in Parkinsonís disease.
Our central hypothesis is that increased ketone production induced through dietary carbohydrate restriction will cause a reduction in abnormal accumulation of the protein alpha-synuclein in the brain and improve motor and cognitive function in pre-clinical models that over produce human alpha-synuclein.
Experimental models that overproduce the protein alpha-synuclein, a genetic model of Parkinsonís disease, and models that produce normal amounts of alpha-synuclein will be fed either a low-carbohydrate diet or a control diet for 28 days starting at two months of age. After, all models will be tested for motor, attention and memory function. Following behavior testing, we will measure ketone levels in blood and abnormal accumulation of the alpha-synuclein in brain. In addition, proteins involved in the breakdown of alpha-synuclein will be measured in the brain.
Impact on Diagnosis/Treatment of Parkinsonís Disease:†
The low-carbohydrate diet, also known as the ketogenic diet, is already used clinically in children with epilepsy. Therefore, it is an established safe application in people and would be easily applied to Parkinsonís patients.
Next Steps for Development:
The next important steps will be to test the long-term effect of the ketogenic diet on behavior and abnormal alpha-synuclein and to test whether administration of ketones alone can improve behavior and reduce abnormal alpha-synuclein.
Assistant Professor at University of Cincinnati
Location: Cincinnati, Ohio, United States