Finally, a Promising Treatment for Alzheimer's?

Alan R. Jacobs, MD


January 30, 2018

This is the Medscape Neurology Minute. I'm Dr Alan Jacobs.

Researchers from Massachusetts General Hospital, in conjunction with the University of California, San Diego, have published a study analyzing the mechanism by which gamma-secretase modulators reduce levels of amyloid-beta 42, the primary pathologic driver of Alzheimer disease.[1]

Previously this group had developed a class of soluble 2-aminothiazole gamma-secretase modulators (SGSMs) that preferentially decrease amyloid-beta 42 levels and leave alone the normal processing of other cellular proteins.

Now they used a representative of this class, called SGSM-36, in animals and cell lines expressing familial Alzheimer disease mutations. They showed that SGSM-36 preferentially reduced amyloid-beta 42 levels, without affecting either alpha- or beta-secretase processing of amyloid precursor protein or Notch processing.

They also identified an allosteric site within gamma-secretase that allowed access of SGSM-36 using imaging microscopy.

The authors concluded that this SGSM class shows great therapeutic potential in Alzheimer disease.

This has been the Medscape Neurology Minute. I'm Dr Alan Jacobs.


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