Neurodegenerative diseases: immunotherapy, biomarkers, clinical and epidemiological investigations
Swedish Research Council
Alzheimer´s disease (AD), dementia with Lewy bodies (DLB) and Parkinson´s disease (PD) are the most common neurodegenerative disorders caused by aggregation of pathological proteins in the brain. In AD, amyloid-beta is deposited extracellularly whereas in DLB and PD alpha-synuclein accumulates in nerve cells and cell membranes. To date, there are no therapies against the respective pathogeneses, although immunotherapy against amyloid-beta has shown some promise in clinical trials on AD patients. However, an optimal therapy should target soluble protofibrils of amyloid-beta, which are likely to be the most toxic forms. We have therefore developed a protofibril selective monoclonal antibody, mAb158, which has been well tolerated in a phase I clinical trial. We now aim at further improving amyloid-beta directed immunotherapy. Moreover, to develop a targeted immunotherapy also for PD and DLB we have generated antibodies highly selective for alpha-synuclein protofibrils. As there also is a lack of reliable disease biomarkers, we are generating assays that can measure protofibrils of amyloid-beta and alpha-synuclein. We are performing clinical and epidemiological studies to evaluate these novel biomarkers in cerebrospinal fluid. In addition, we are developing a new type of PET ligand selective for amyloid-beta protofibrils. The significans of this program is that we are developing new treatments and biomarkers for neurodegenerative diseases.