Intermittent treatment with farnesyltransferase inhibitor and sulforaphane improves cellular homeostasis in Hutchinson-Gilford progeria fibroblasts.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory cell culture experiment with no human or animal subject data
PubMed 29029393 · doi:10.18632/oncotarget.19363
What was done
Researchers tested the effects of combining the farnesyltransferase inhibitor lonafarnib with sulforaphane in cultured Hutchinson-Gilford progeria syndrome (HGPS) fibroblasts. They evaluated both simultaneous co-administration and intermittent, sequential treatment regimens (lonafarnib followed separately by sulforaphane in repeated cycles) on autophagy activity, cytotoxicity, and cellular phenotype rescue.
What was found
The abstract reports directional findings without numerical values. Co-administration of lonafarnib and sulforaphane showed a synergistic and additive positive effect on autophagy activity but was cytotoxic to HGPS fibroblasts. In contrast, intermittent sequential treatment with lonafarnib followed by sulforaphane in repeated cycles rescued the HGPS cellular phenotype.
Why it matters
Lonafarnib is used clinically for progeria and sulforaphane stimulates progerin clearance, but simultaneous combination is toxic in vitro. Demonstrating that intermittent sequential delivery rescues cellular phenotypes without cytotoxicity suggests a dosing strategy to explore for progeria therapeutics.
Limits
This is an in vitro cell culture study with no animal or human subject data. The abstract provides no quantitative metrics, statistical values, sample sizes, cell line counts, or drug concentrations.
Cited by
- supports Karima Djabali's research group demonstrated that sulforaphane reverses the cellular phenotype in progeria models.