24 replies to this topic

[Happycat]

Well, I've got plenty of feverfew preparation (called Migrelief) for the dd's migraines.  Now I've got a better idea of why it didn't work that well for her, poor bioavailability.  Too bad I can't use it for me, since I've got about 6 bottles of it sitting around.

Traci

[cousineg]

Another article about parthenolide:

Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.

June 15, 2008, PubLMed

[Trey]

It should also be noted that the Parthenolide discussions center on AML leukemia, not CML.  The reason is that AML starts with lower level stem cells (more likely progenitor cells) than CML.  So the cellular processes which can be disrupted to affect the disease are different in CML than for AML.  Also, AML does not have any truly effective drugs that work on leukemic progenitor cells, but CML does have such drugs.  So for CML, Parthenolide will not do much more than TKI drugs, and very likely will not control CML nearly as well.

[Sandrea]

In vivo targeting of leukemia stem cells by directing parthenolide-loaded nanoparticles to the bone marrow niche     Leukemia. 2016 Jul; 30(7): 1582-1586.

This study demonstrates the efficacy and utility of encapsulating unmodified pre-clinical small molecules such as parthenolide (PTL) in a multistage vector system (MSV) to facilitate delivery to the tumor niche. LSCs reside within and are protected by the  bone marrow (BM) niche. Encapsulation of PTL into the MSV coated with ESTA resulted in rapid delivery of chemically intact PTL to the BM niche. Two doses of MSV-PTL delivered two weeks apart were capable of reducing AML burden and dramatically impairing LSC function in vivo. The poor bioavailability and pharmacokinetic profile of PTL were overcome by encapsulation in the MSV, producing in vivo efficacy against LSCs using AML-PDX mice. Indeed, PTL delivered via this system engaged cellular responses consistent with PTL activity, leading to a decrease in both AML burden and LSC function. Overall, these studies demonstrate that the use of targeted MSV nanoparticles is a novel and promising therapeutic approach in AML by facilitating anti-LSC small molecules such as PTL to the BM niche.
The authors are supported by Leukemia and Lymphoma Society.

[missjoy]

PTL and CML

http://www.bloodjour...so-checked=true