Antibody Therapy to Block Alpha-Synuclein Spread and Toxicity
Target Advancement Program, 2017
Parkinson's disease (PD) is characterized by the accumulation of misfolded pathologic alpha-synuclein. This toxic alpha-synuclein moves between neurons and causes progressive neuronal death. Blocking entry of the toxic alpha-synuclein into neurons with an antibody (immune protein) can prevent the progression of neuronal cell death.
Does blocking entry of toxic alpha-synuclein into neurons with an antibody prevent neuronal cell death and slow or block disease progression?
A misfolded version of alpha-synuclein will be injected into pre-clinical models. The models will also be injected with antibody 410C9 or a control antibody into the receptor on neuronal surfaces that draw the toxic alpha-synuclein into a healthy neuron, where it then kills the neuron. Models will be aged until they exhibit parkinsonian behaviors and pathology. The effects of the active 410C9 antibody will be evaluated for protection against the development of parkinsonian behaviors and pathology.
Impact on Diagnosis/Treatment of Parkinson's disease:
If the 410C9 antibody protects pre-clinical models from developing parkinsonism behaviors and pathology following injection of toxic alpha-synuclein, this antibody may advance into clinical trial testing.
Next Steps for Development:
The antibody would first need to be "humanized" so that the human immune system would not reject it. Safety and toxicity studies would also need to be performed. The Food and Drug Administration would then need to approve the antibody prior to use in a clinical trial.
Professor and Director of the Neuroregeneration and Stem Cell Programs at the Institute for Cell Engineering at Johns Hopkins University School of Medicine
Location: Baltimore, Maryland, United States