2020 Volume 55 Issue 1 Pages 1-5
The population of dementia sufferers is estimated to reach 152 million in 2050. Dementia lays a huge burden on family members, medical staff and caregivers in addition to the sufferers themselves, and could possibly collapse the current social system. To prevent such a catastrophe, drug discovery to fight dementia is an urgent task that should be undertaken by all humanity as the 21st-century equivalent of traveling to the moonshot. Alzheimer’s disease (AD) accounts for more than 50% of total dementia, and its three major pathologies are known to be senile plaque composed of amyloid beta (Aβ) aggregates, neurofibrillary tangle made by tau protein aggregates, and neuronal cell death commencing with cholinergic neurons. AD pathogenesis is being elucidated through pathology, genetics and biology, and these studies have led to three hypotheses. Approaches under the choline hypothesis created three acetylcholine esterase inhibitors (donepezil, rivastigmine, and galantamine) which enhance cholinergic neuronal activity. These three medicines and memantine (NMDA antagonist) are currently available for AD treatment. They temporarily improve cognitive and daily functions but cannot slow down the progression of AD itself. Aimed at disease modification, a number of agents based on the Aβ hypothesis have been investigated in clinical studies, but most of them have failed. Currently a few anti-Aβ antibodies are in the final stage of clinical trials and are expected to be commercialized in the near future. Following on from anti-amyloid therapy, multiple approaches including tau, microglia and synaptic/neuronal regeneration are being actively researched to cure this complex disease. In parallel with drug discovery, less-invasive diagnostics that realize earlier detection and intervention are also being developed and have shown significant progress over the last two years. I believe that dedicated endeavors by the scientists working in the AD field and the thoughtful support of patients in society will bear fruits to actualize healthy longevity by conquering dementia.
