3 replies to this topic

[resveratrol_guy]

"In the [cancer] patients that received a colony-stimulating factor (CSF) to stimulate the bone marrow and recover immune system function, we found that those who received GM-CSF (Leukine®/Sargramostim) plus G-CSF (Filigrastim) significantly improved in cognitive function as compared to those who received G-CSF alone."

 

Wikis: GMCSF, GCSF.

 

As covered in my own stem cell microtrial thread and backed by at least one published study, GCSF seems to promote improved cognition with persistent effect. Back in 2012, it was shown in this study (see the numbers in this graph) that its effects may occur over a protracted period of 12 months, yet appear to be clinically significant in magnitude. (Granted, this study was done on cancer patients, so I hypothesize that GCSF benefits occurred more rapidly, but were masked by the side effects of chemotherapy for several months.) Nevertheless, this same study demonstrated that GMCSF (GM-CSF, granulocyte macrophage colony stimulating factor) both enhanced and accelerated the onset of clinical improvement. GMCSF is sold in the US as its FDA-approved analog, Leukine (sargramostim). (The FDA approval was for uses other than dementia.)

This is all very ironic because a 2009 mouse study showed that neutralizing GMCSF decreased amyloid load in mice. Perhaps this is nothing more than yet another disconnect between murine and human physiology, but it's worth noting because GMCSF might have U-shaped efficacy against Alzheimer's, wherein extreme amounts are beneficial, but normal amounts permit disease progression.

Now, as of 1/30/2015, this phase 2 clinical trial of Leukine for Alzheimer's is recruiting patients. (Phase 1 was initiated in 2011, shortly before the aforementioned paper was published.) They are testing Leukine in isolation; a GCSF analog will not be provided (and perhaps is unnecessary).

The original Alzheimer's GMCSF thread was last active in 2010, bourne out of an epidemiological analysis which revealed a negative correlation between rheumatoid arthritis and Alzheimer's. Note that nutrition affects endogenous GMCSF production as noted in this thread. (I didn't post that one, despite the similar username.) Perhaps the cognitive benefits of blueberry consumption are related more to GMCSF than pterostilbene or anthocyanin. In any event, I don't think it's possible to mimic the impact of Leukine merely by dietary modification.

 

Edited by resveratrol_guy, 28 February 2015 - 06:23 PM.

[resveratrol_guy]

Caveat: resveratrol appears to inhibit endogenous GMCSF in this study, at least as far as human airway smooth muscle cells are concerned. This is odd, considering that both appear to be antialzheimer's. "resveratrol reduces basal and IL-1β- and cigarette smoke-induced release of IL-8 and GM-CSF" -- maybe resveratrol merely reduces the inflammation upstream from GMCSF, thereby obviating the need for its secretion. Anyway, I don't pretend to understand the significance of this apparent contradiction, but thought I should share it.

 

Also, I'm thinking that maybe that exogenous GMCSF will cause the mobilization of microglia (obviously), but if coadministered with a proinflammatory cytokine antagonist (lipidated curcumin or others), would do so with less inflammation. In other words, the supposed benefit of GMCSF therapy might be further enhanced in this manner. After all, if we mobilize enough microglia (easily done with Leukine), then it won't be necessary for them to attract their friends using these inflammatory signaling proteins. The analogy would be a thousand people in a football stadium picking up trash; with so many people, they need not communicate much in order to clean the field effectively. So we get the macroautophagy without the inflammation.

 

Edited by resveratrol_guy, 14 March 2015 - 03:39 AM.

[resveratrol_guy]

Uh oh! Being resveratrol_guy might explain my history of memory problems.

 

[Der Springende Punkt]

Didn't see this thread as I posted the positive clinical trial data of Leukine in The Latest Alzheimer's Research thread:

 

 

Positive data from a small safety trial of Leukine (sargramostim / GM-CSF) reported at AAIC in London.

 

 

“This is a short safety trial, lasting just under three weeks for each participant, and we weren’t expecting to see improvements in cognitive testing results,” said Dr. Boyd, who has been working with Dr. Potter on the Alzheimer’s treatment theory involving Leukine® since 2007. “For us to see these kinds of improvements gives us a lot of hope.”

 

Dr. Potter said thinking and memory indicators were tested using the Mini-Mental State Examination (MMSE), a common evaluation tool in dementia diagnostics. At the end of treatment, the participants improved their baseline scores by a statistical measurement considered “significant.”  When the same test was administered weeks after the treatment phases ended, the scores returned to levels closer to baseline.

 

 

@resveratrol_guy: Do you know of any ways to stimulate GM-CSF without getting arthritis and injecting Leukine?