Another Look at Failed Alzheimer Disease Drug Trial

Alzheimer’s disease is a condition characterized by progressive dementia affecting cognition, behavior, and functional status. Symptoms tend to appear gradually and progressively. The exact etiology of Alzheimer's is unknown, and therefore, no cure exists. The CDC estimates that Alzheimer's was the sixth-leading cause of death in the US in 2015, and in 2014, 50.4% of nursing home residents were diagnosed with the disease. Tools, such as imaging studies (computed tomography scan, magnetic resonance imaging, and positron emission tomography), laboratory tests (thyroid function and vitamin B12 test), and neurological examination (ADAS-cog14, ADCS-iADL, CDR-SB, FAQ, and MMSE, per the American Academy of Neurology), are used to diagnose Alzheimer's and prescribe drug therapy.

Pharmacotherapy focuses on improving cognition, behavioral symptoms, and functional ability. FDA-approved therapies include NMDA receptor antagonist and cholinesterase inhibitors in order to slow the progression of Alzheimer's and symptomatic management.The American Academy of Family Physicians and the American College of Physicians suggest that memantine has modest benefits in patients with moderate to severe Alzheimer's. In advanced Alzheimer's, a combination of AChEI (donepezil, galantamine, and rivastigmine) and memantine is suggested.Scientists have discovered that Alzheimer's is characterized by the formation of beta amyloid plaques, gliosis, and neurofibrillary tangles.

Therefore, there has been an increasing effort to target such properties via pharmacotherapy. Solanezumab is an investigational humanized monoclonal antibody that works by binding and increasing the clearance of the beta amyloid from one’s brain. Solanezumab has failed to significantly affect cognitive decline compared with the placebo in subjects with mild Alzheimer's.

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