Table 1.
Clinical implications of candidate Aβ regulatory pathways
| Pathway | Candidate Materials (examples only) | Comments |
|---|---|---|
| Kinase modification | Perifosine, Keryx (Gills and Dennis, 2009); CEP–1347, Cephalon (Wang and Johnson, 2008) |
This pathway would allow use of drugs already developed. Potential for unexpected side effects due to wide activity profiles for target kinases; Low efficacy in clinical trials |
| Chelation | PBT2, Prana (Adlard, et al., 2008, Ritchie, et al., 2004) | Parent compound Clioquinol implicated in the disorder SMOM in large doses; PBT2 lower side effects |
| Cholesterol metabolism modification | Simvastatin, Merck (Tong, et al., 2009); D–4F, Novartis (Handattu, et al., 2009); Dietary modification (Pallebage-Gamarallage, et al., 2009) |
Some agents already well–characterized for tolerability Dietary modification avoids drug therapy |
| Secretase modification | CTS–21166, CoMentis (Panza, et al., 2009); LY450139, Lilly (Bateman, et al., 2009); Etazolate, ExonHit (Marcade, et al., 2008) |
Long–term effects of secretase modification unknown; Potential for interference in similar pathways (e.g., Notch vs. γ–secretase) |
| Aβ as a transcription factor | siRNA to Aβ–binding sites in target promoters; Antisense DNA to Aβ–binding sites in target promoters |
Potential for high specificity (low side effects); Speculative; Little to no current clinical use |