Cinaciguat Halves Alzheimer's-Linked Protein in Rats — SkimNews
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- Cinaciguat restored the structure and function of liver sinusoidal endothelial cells (LSECs) in aged rats after two weeks of treatment, reopening the sieve-like pores that shrink with age and normally let blood-borne molecules reach hepatocytes.
- Amyloid beta concentrations in treated older rats fell by approximately 50% to levels comparable with young rats, while untreated older rats showed no similar improvement.
- LDL cholesterol dropped to levels seen in young animals in the same treated older rats — a result researchers did not expect, since LDL had been included only as a comparison measure and does not exit the blood through LSEC pores.
- HB-EGF, a growth factor released by LSECs after cinaciguat activates soluble guanylate cyclase, was identified as a previously unknown signal that prompts neighboring hepatocytes to capture more LDL and amyloid beta from the blood.
- Journal of Biological Chemistry published the study, which the researchers describe as the first demonstration that a drug can fully restore the structure and function of aging LSECs and the first liver-directed treatment to bring age-related elevations of circulating amyloid beta and LDL back to youthful levels.
- Sam de Leve, first author and a USC lab technician, proposed targeting the liver rather than trying to get drugs through the blood-brain barrier, the obstacle the source links to an estimated 98% clinical-trial failure rate for brain-directed Alzheimer's treatments.
- Laurie DeLeve, corresponding author and a USC Department of Medicine professor, said the rat results need further translational work to establish whether the benefits occur in humans; the source notes lower blood amyloid beta does not necessarily mean fewer brain plaques or prevented Alzheimer's.
Why it matters: For Alzheimer's drug developers, the appeal is a route the source notes brain-targeted efforts have failed at an estimated 98% of the time: act on the liver instead of trying to cross the blood-brain barrier. Sam de Leve also says atherosclerosis researchers now have "six different ways" to pick up the idea.
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