New Alzheimer's treatment on the horizon

From the BBC:

Experimental drugs are being hailed as a potentially exciting step forward in the treatment of Alzheimer's. The drugs, still in clinical trials, form a new class called gamma-secretase modulators (GSM).

Here's the deal. (One of) the main morphological markers of Alzheimer's disease (AD) is the extracellular formation of amyloid beta plaques. It is thought that blocking their formation may prevent, or at least delay, the development of this neurodegenerative disease. Here is how the plaques get formed in the first place:


The amyloid precursor protein (APP) is cleaved by two enzymes: beta and gamma secretase. In Alzheimer's, it is believed that something goes wrong with these enzymes resulting in a larger than normal amyloid beta protein (42 rather than 40 amino acids), which leads to plaque formation. So, inhibit the enzymes and you prevent AD, right? Well, this seems to be reasonable, and research is underway with beta-secretase inhibitors. But, the problem is that gamma secretase also cleaves other proteins; specifically, it cleaves Notch-1, which is important for cell development and growth. Hence, gamma inhibitors have not had a good track record. However, this is a gamma-secretase modulator* so it may not have the same unintended effects as the inhibitors.


(image via St. Johns' University)

* Actually, it seems that it is unclear exactly how these drugs are acting, via gamma-secretase or directly on the amyloid beta protein or both.