Objective/Rationale:
Parkinson’s is associated with an inflammatory response, which in the brain is mainly mediated by cells called microglia. Inflammation is normally beneficial helping us fight infections, but excessive inflammation can cause damage nerves by releasing toxic factors. TLR-2 receptors are one of the receptors responsible for the activation of microglia and release of toxic factors, levels of TLR-2 are increased in Parkinson’s and hence represent an excellent drug target to inhibit inflammation and prevent further cell loss.
Project Description:
Opsona has developed an antibody that will block the TLR-2 receptor for the potential treatment of diseases like rheumatoid arthritis but could it also treat Parkinson’s. At the present time, the antibody does not cross into the brain. Hence, during this “proof of concept study” the TLR-2 receptor antibody will be administered directly into the brain. The neuroprotective effects of the antibody will be tested in two animal models of Parkinson’s. We will not only look to see whether the TLR-2 receptor antibody prevents the development of Parkinson like behavior in the models but we will also test whether it prevents the neurons from dying. Blocking the TLR-2 receptors should block the inflammatory process, which is also a feature in the animal models, hence we will also examine whether the antibody therapy reduces the inflammatory reaction.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If the TLR-2 receptor antibody proves to be neuroprotective it will ultimately be redesigned so that more easily enter the brain. After further confirmatory studies it animals, the modified antibody could be tested clinically where it would it could potentially prevent further neuronal loss in Parkinson’s patients. The initial impact would potentially to prevent the progression of Parkinson’s. In the future if were to be able to predict who will develop Parkinson’s, the antibody may help prevent the development of Parkinson’s.
Anticipated Outcome:
The anticipated outcomes will be two-fold. Firstly, the results of the study will increase our knowledge as to whether inflammation plays a role in neuronal cell loss in Parkinson’s. Secondly, the results will support the concept that blocking the TLR-2 with antibodies reduces the inflammatory response in the models of Parkinson’s and whether this approach will ultimately prevent the loss of neurons. Thus data will support the future development of this therapeutic approach.