Recent history has not been kind to R&D efforts aimed at developing new Alzheimer's drugs. While four approved drugs can help manage symptoms of the disease, and perhaps slow its progression to a small degree, the field has aggressively pursued new treatments that can significantly slow or stop progression.
These efforts have been hampered by the complexity of the disease and by, what most experts consider, a fairly rudimentary understanding of its pathology. We understand that Alzheimer's disease manifests as a decline in cognitive function, and that the decline is caused by a loss of brain cells and the connections between them. We also understand that an accumulation of amyloid proteins in the brain, and a chemical change in Tau proteins (phosphorylation) in the brain, are major factor contributing to that loss of brain cells.
However, the picture becomes less clear when we try to identify the many possible processes that start the pathology. The answer may be related to cell metabolism, to brain chemistry, to inflammation, or trauma, just to name a few of the leading areas of scientific inquiry. Probably, a host of these processes interact and lead to a cascade of biological responses along the way.
The questions to which we do not yet have solid answers are: which processes matter most, are they inter-related, and why do they lead to this disruptive outcome? Without those answers, it is difficult to develop drugs that will target the right process, at an early stage. It is a very complex problem involving the most complex of organs.
Nonetheless, research persists and scientific efforts are ongoing. At this point, several promising agents are moving along the pathway in FDA clinical trials. A good overview of the Alzheimer's pipeline was recently published by Fierce Biotech. It is slightly technical, and geared toward financial analysts, but it is comprehensive and gives a good foundation of the theory behind each approach.
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