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[Logic]

This study is about slowing/stopping Progeria in mouse models of Progeria and children with Progeria using re-purposed cancer drugs.
IIRC, the amount of progerin protein in one's system increases with normal aging, with the same deleterious effects as those seen in Progeria sufferers.

So these drugs are of interest to us.  Especially older members and those with cardiovascular problems.

 

Tipifarnib and Lonafarnib, are the two Farnesyltransferase/Progerin inhibiting cancer drugs re-purposed for this study.

"Although their efficacy in human (phase III) clinical cancer trials has been somewhat disappointing, both FTIs have proven to be remarkably well tolerated..."

 

 

A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model

Hutchinson-Gilford progeria syndrome (HGPS) is the most dramatic form of human premature aging. Death occurs at a mean age of 13 years, usually from heart attack or stroke. Almost all cases of HGPS are caused by a de novo point mutation in the lamin A (LMNA) gene that results in production of a mutant lamin A protein termed progerin. This protein is permanently modified by a lipid farnesyl group, and acts as a dominant negative, disrupting nuclear structure. Treatment with farnesyltransferase inhibitors (FTIs) has been shown to prevent and even reverse this nuclear abnormality in cultured HGPS fibroblasts...

 

...Accumulating in vitro and in vivo data has indicated that FTIs may in fact offer some hope for patients with HGPS...

 

...The discovery that the mutant lamin A protein in HGPS (i.e., progerin) is permanently modified by a lipid farnesyl group, and that this appears to act as a dominant negative, pointed toward a possible therapeutic target. This target emerged as a particularly attractive one because of the existence of already well tested inhibitory compounds, the FTIs. Currently two such orally administered FTIs are in phase III clinical trials for cancer, motivated originally by the observation that the oncoprotein Ras is farnesylated. Although their efficacy in human clinical cancer trials has been somewhat disappointing, both FTIs have proven to be remarkably well tolerated...

http://www.ncbi.nlm....les/PMC2562418/

 

Progeria links:

http://www.longecity...2α-in-progeria/

http://www.longecity...tures-of-aging/

http://www.longecity...-prevent-aging/

http://www.longecity...ndpost&p=744460

To do:

As the paper is from 2008 the results of the phase III trials should now be available.

Check the availability of Tipifarnib & Lonafarnib and their side effects etc.

 

(WTF is up with all the ....Nibs? Tipifarnib, Lonafarnib, Nilotinib, Dasatinib...?)
 

 

 

[Logic]

A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model

...Currently two such orally administered FTIs are in phase III clinical trials for cancer, motivated originally by the observation that the oncoprotein Ras is farnesylated. Although their efficacy in human clinical cancer trials has been somewhat disappointing, both FTIs have proven to be remarkably well tolerated...

http://www.ncbi.nlm....les/PMC2562418/

 

Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia

...Measurements of inhibition of farnesylation of the chaperone protein HDJ-2 in marrow blasts obtained on day 8 of tipifarnib therapy revealed an increase in unfarnesylated protein in 75% of marrow samples, while inhibition of farnesylation of the nuclear membrane protein Lamin A could be detected in 92% of all concomitantly-obtained samplers of buccal mucosa...

...the potential impact of FTIs on other disease processes is presaged by the ability of ABT-100 to ameliorate the process of premature aging in a mouse model of progeria which, like the human condition, is characterized by accumulation of an abnormally farnesylated form of the lamin A precursor prelamin A, disruption of orderly nuclear scaffolding, and resultant misshapen nuclei...

http://www.ncbi.nlm....les/PMC2721391/

 

Lonafarnib: promising results in first-ever trial for progeria

...Preclinical studies have shown that the combination of pravastatin and zoledronic acid reversed abnormalities of the nucleus in transgenic mice expressing progerin, as well as in cultured cells from human patients with progeria...

 

...Noteworthy improvements in the study population included a greater than 50 per cent increase in the annual rate of bodyweight gain, or a switch from weight loss to weight gain, in one in three children due to significant increases in muscle and bone mass; improvement of bone rigidity to normal levels; a median 35 per cent decrease in arterial stiffness; and improvement in blood vessel wall density following FTI treatment...

 

...Continued study of this disease is hoped to further understanding into human ageing in general. Lamin A defects are also associated with normal ageing, and research has shown that low levels of progerin are produced in all humans and accumulate with age...

http://www.pmlive.co...al_for_progeria

Edited by Logic, 07 February 2016 - 09:01 AM.