Q: What did we learn?
We know that Abeta oligomers, a “seeding species” in Alzheimer’s disease, are predominantly spread in the brain via naked protein aggregates, and not through extracellular vesicles.
Q: Why is this knowledge important?
The development of oligomer-specific antibodies (Acumen, ProMIS Neurosciences) has enabled selective immunotherapies for Alzheimer’s disease that target the toxic molecular species of AD, while sparing precursor protein (APP), Abeta monomers, and Abeta fibrils in the form of plaques. Binding to any of these non-oligomer molelcular species of Abeta lead to adverse effects, most prominently plaque-disruption linked ARIA – a form of neurovascular brain edema.
Q: What are the next steps?
Dr. Cashman is now the full-time Chief Scientific Officer of ProMIS Neurosciences, which is conducting IND-enabling studies of the oligomer-specfic antibody PMN310. Human phase 1 trials are set for late 2022 or Q1 2023.
PUBLICATIONS
Links to articles, papers and presentations connected this work:
https://pubs.acs.org/doi/abs/10.1021/acschemneuro.7b00469
https://www.nature.com/articles/s41598-019-46306-5
ABSTRACT
A treatment or prevention of Alzheimer’s disease is a top priority for medical science. Small aggregates of the protein amyloid-beta (A-beta), called oligomers, have been identified as being the primary cause of brain cell death in Alzheimer’s disease. We have identified an A-beta oligomer-specific targeting site, which exclusively detects A-beta oligomers in the brains and spinal fluids of Alzheimer’s disease patients. Since we only found A-beta oligomers with our targeting site in the brains of Alzheimer’s disease patients, it is possible that we have defined a targeting site specific to the A-beta oligomers that cause disease. We will exploit this new knowledge and our unique tools to learn how toxic A-beta oligomers spread from region-to-region in the brain causing disease. This knowledge is critical for the development of therapeutics to block the spread of neurodegeneration in the brain.