A vaccine designed to protect against Alzheimer's disease has passed the first stage of clinical trials. It joins many other proposed dementia treatments, all jostling to ease the fears of an aging population, but targets a different aspect of the disease. Its designers think this may see it avoid the side-effects that have halted many other trials.
In Lancet Neurology a team led by Dr Petr Novak of AXON Neuroscience, Slovakia, has announced the vaccine induced the desired immune response in 29 of 30 patients with mild-to-moderate Alzheimer's. Two showed serious health effects, not necessarily related to the vaccine.
Alzheimer's disease is by far the most common cause of dementia. Longer lifespans are anticipated to see developed world rates triple by 2050. The race for treatment is hampered by limited understanding of the causes.
In particular, there is disagreement between neuroscientists who blame the beta amyloid plaques that are the disease's most obvious effect on the brain (sometimes called BAPtists), and those who consider tau proteins to be more important. The latter group, inevitably dubbed Tauists, consider tangles of tau protein appearing within brain cells the more serious cause of dementia, and usually consider the plaques a distraction.
Historically, the majority of research has focused on the plaques, leading to several trials of drugs that showed promise in animals, some of which were discontinued after serious human side effects.
Novak and his co-authors believe these trials failed, not just because they targeted the wrong part of the Alzheimer's complex, but because amyloid has other roles in the brain, and the drugs hit this too. Consequently, they took care to distinguish the “pathological tau” tangles and healthy versions of the protein that exist in everyone's brains.
Having identified a region of pathological tau that is absent in the normal version of the protein, the researchers sought an antibody that would target this region alone. The vaccine successfully stimulated this antibody, raising hopes it might clean up the tangles.
The researchers are excited by the fact that, unlike anti-plaque drugs, their treatment did not induce inflammation or fluid on the brain.
“This is the first active vaccine to harness the body’s ability to produce antibodies against pathological tau," said co-author Professor Bengt Winblad, also of AXON, in a statement. "Even though this study is only a phase 1 trial, its success so far gives the authors confidence that it may be the answer they are looking for to halt the progress of this devastating disease.”
The trial was not designed to study the progress of dementia symptoms, but the authors noted that the patients' performance on cognitive tests remained stable during the 12-week trials. Phase II trials are underway, with results anticipated in 2019.