Re-distribution of Brain Gangliosides for Treatment of Parkinson's Disease
Rapid Response Innovation Awards, 2007
A pre-clinical model of Parkinson's disease can be generated by injecting MPTP, a toxin that results in specific damage to the same part of the brain that is damaged in Parkinson's disease. The proposed experiments will examine the effects of this toxin in mice with full or partial elimination of GD3S. mice will first be assessed on a batter of behavioral tasks designed to assess Parkinson-like impairments, and will then be injected with MPTP. Additional behavioral batteries will be conducted to assess the motor effects of MPTP injections. Mice will then be sacrificed, and brains assayed for cell death.
Relevance to Diagnosisflreatment of Parkinson's Disease:
Typical treatments for Parkinson's disease focus on replacement of the dopamine or dopamine-producing cells that are lost. A new treatment that has shown promise in Parkinson's patients is the administration of GM1 ganglioside. Elimination of GD3S has the effect of increasing the body's own levels of the neuroprotective GMl ganglioside, while at the same time eliminating the potentially toxic GD3 ganglioside.
We expect to show that mice completely lacking GD3S (GD3S-/-) are completely resistant to MPTP-induced cell death and exhibit normal mouse motor behaviors. Based on preliminary data fi-om our lab and others, we also expect to see substantial neuroprotection in mice heterozygous for GD3 S (GD3 S+/-).
Assistant Professor of Pharmacology at University of Tennessee
Location: Memphis, Tennessee