The serum form of amyloid P component (SAP) is believed to bind to neurofibrillary tangles and amyloid deposits in the cerebrovascular fluid. Since beta amyloids are the main constituents of plaque in Alzheimer’s patients and SAP stabilizes them and promotes their persistence, inhibiting SAP may be an indirect method to prevention or restoration in Alzheimer’s disease.
Kolstoe et al recently discussed their novel drug, (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), which is small but which can still act as a ligand for SAP by competitively inhibit its binding to beta amyloids. In their pilot study 5 patients with risk factors for Alzheimer’s disease aged 53-67, SAP concentration fell from 32.4 +/- 8.4 mg/L to only 0.25 +/- 0.16 mg/L after one week of drug administration. It remained there for as long as the drug was administered but the SAP concentration returned to baseline once CPHPC administration ended.
Since there have been no deleterious side effects demonstrated over a two year period of CPHPC in a separate study, this is a fascinating drug with some real clinical potential. One of the reason for the effectiveness of AIDS drugs has been that doctors can administer a cocktail of drugs, each which target a different aspect of the virus’s propagation. Perhaps a similar approach would be effective in Alzheimer’s, in which case CPHPC could play a prominent role. Of course more trials will be necessary to test these speculations.
Kolstoe SE, et al. 2009 Molecular dissection of Alzheimer’s disease neuropathology by depletion of serum amyloid P component. PNAS 106: 7619-7623. doi: 10.1073/pnas.0902640106.