Amyloid hypothesis and drug development for Alzheimers disorder: A critical review

2018 ◽  
Vol 08 ◽  
Author(s):  
Oleg V Tcheremissine
Author(s):  
P.S. Aisen

The Phase 3 aducanumab program in early AD has been stopped based on a futility efficacy analysis. This huge disappointment follows exciting preliminary studies that had raised expectations (1). Now this frustrating result joins the long series of negative and interrupted trials of potential disease-modifying agents, going back to tarenflurbil (2), tramiprosate (3), and bapineuzumab (4), among many others. Is the amyloid hypothesis wrong? Where do we go from here?


Author(s):  
P.S. Aisen ◽  
E. Siemers ◽  
D. Michelson ◽  
S. Salloway ◽  
C. Sampaio ◽  
...  

Although the results were disappointing from two recent clinical trials of amyloid-targeting drugs in mild-to-moderate AD, the trials provided information that will be important for future studies, according to the EU-US CTAD Task Force, which met in November 2017 to discuss the EXPEDITION3 and EPOCH trials. These trials tested two of the predominant drug development strategies for AD: amyloid immunotherapy and BACE inhibition in populations largely composed of mild AD dementia patients. The results of these trials support the emerging consensus that effective amyloid-targeted treatment will require intervention in early, even pre-symptomatic stages of the disease. Further, the Task Force suggested that a refinement of the amyloid hypothesis may be needed and that other hypotheses should be more fully explored. In addition, they called for improved biomarkers and other outcome assessments to detect the earliest changes in the development of AD.


2021 ◽  
Author(s):  
Manuela Oliverio ◽  
Monica Nardi ◽  
Maria Luisa Di Gioia ◽  
Paola Costanzo ◽  
Sonia Bonacci ◽  
...  

Semi-synthesis is an effective strategy to obtain both natural and synthetic analogues of the olive secoiridoids, starting from easy accessible natural compounds.


Sign in / Sign up

Export Citation Format

Share Document