Tetrapyrroles as anti-amyloidogenic drugs in the treatment of transmissible spongiform encephalopathies

Abstract

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative conditions, currently without treatments. The common underlying feature of these diseases is the accumulation of an abnormal isoform (PrP^Sc) of a host-encoded neuronal cell surface sialoglycoprotein (PrP^C). This accumulation and the tendency for resultant amyloid formation may be the primary pathological event in TSEs and the production, accumulation and deposition of PrP^Schave become the major focus of therapeutic interest. This particular patent concerns the possible therapeutic usefulness of tetrapyrroles. Various tetrapyrroles have been evaluated in cell-free, cell culture and whole animal experiments, using a hamster-adapted strain of scrapie. Significant benefit has been demonstrated in these experimental models, suggesting therapeutic promise for these drugs. However, no evidence is provided for effectiveness with other prion strains, in particular, for strains related to human diseases. There is also no evidence concerning effectiveness in treating clinically established disease and no evidence concerning long-term safety in humans. The patent makes unsupported extensions of these claims to untested members of the same group of compounds and to their use in other neurodegenerative conditions such as Alzheimer’s disease. Nevertheless, this patent includes data indicating that tetrapyrroles are leading anti-amyloidogenic candidates for the treatment of TSE.

• amyloid
• CJD
• prion
• PrPC
• PrPSc
• tetrapyrroles
• transmissible spongiform encephalopathies