. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002 May 16;417(6886):254-9. PubMed.


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  1. This is a beautiful paper that follows a large body of excellent work from these investigators. However, no data is presented as to how the disruption of the interaction between SAP and amyloid fibrils by their drug candidate affects the fate of the amyloid itself. This paper is focused exclusively on the clearance of SAP from the deposits. The authors state that they hope that the clearance of SAP will "reduce the stability of amyloid deposits and promote their regression". This is certainly a reasonable hypothesis, given that other studies have shown amyloid deposits can be cleared and that the SAP knockout mouse showed retarded and reduced disease.

    However, it is very important to note that the systemic amyloidoses discussed in this paper seem to be caused by the amyloid fibrils themselves, whereas the neurodegenerative amyloidoses, including PD and AD, seem to be caused by a fibril precursor, or protofibril. In the latter cases, a molecule that promotes fibril accumulation (and protofibril depletion) could actually slow disease progression by removing the toxic species. Ron Kopito's aggresome model emphasizes that there may be evolved mechanisms to detoxify protein aggregates in the cytoplasm (Kopito, 2000).

    Thus, the strategy discussed here could be very useful for systemic amyloid diseases, but is less likely to be useful for neurodegenerative disease. In fact, it may not be wise to interfere with such an interaction in the latter diseases.


    . Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000 Dec;10(12):524-30. PubMed.

    View all comments by Peter Lansbury
  2. In the paper, serum amyloid P is depleted from plasma with a new drug. While SAP has nothing to do with Abeta (it binds to other amyloids in peripheral amyloidosis), it raises the possibility as to whether one can deplete an Aβ binding protein such as apoE or others as a treatment for AD. Whether one would need to do this in the brain vs. plasma vs. both is not clear.

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