Immunotherapy with Alpha-synuclein Specific Antibody
Synuclein Therapeutic Acceleration Program, 2013
Objective/Rationale: † † † † † ††
The protein alpha-synuclein is believed to play a major role in the development of Parkinsonís disease (PD). Toxic forms of alpha-synuclein can cause neuronal dysfunction and, when secreted from cells, the protein can be taken up by neighboring cells, thereby spreading the disease from one brain region to another. The rationale for this project is that a therapeutic antibody against alpha-synuclein will be able to block its harmful effects, clearing this protein, and thereby preventing the disease from spreading. † † †
Project Description: † † † † † ††
Antibodies binding to alpha-synuclein have been selected in cell models. One of them has shown positive effects in pre-clinical models for PD. The selected antibody will be optimized using antibody engineering techniques to increase its ability to bind and remove alpha-synuclein. These studies will also enable us to evaluate the role of the immune system and minimize potential safety issues. Optimized versions of the parent antibody will be tested in models. The most efficacious antibody will be further tested for safety. In order to translate the model studies into the clinic, we will develop assays to evaluate both antibody levels and alpha-synuclein levels in tissues, blood and spinal fluid.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
Immunotherapy targeting alpha-synuclein is a new way of treating PD. By neutralizing the toxic forms of the protein the antibody has the potential to delay the progression of the disease and prevent spreading of the disease from one brain region to another. We anticipate that this treatment will delay appearance of symptoms and reduce severity of symptoms. Thereby immunotherapy could be the first disease-modifying treatment for PD.
Anticipated Outcome: † † † † †
The studies outlined in the current proposal are designed to generate the most efficacious form of a therapeutic antibody for the treatment of PD. By antibody engineering we will learn about the importance of the strength of antibody binding to alpha-synuclein, and interaction between the antibody and the patientís immune system. We will also learn about the dynamics between antibody drug levels and target levels.† These studies will generate the necessary tools and data required to design a successful clinical trial.
Doctor at H. Lundbeck A/S
Location: Copenhagen, Denmark