Could an Aspirin a Day Keep Multiple Sclerosis at Bay?

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frodo
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Could an Aspirin a Day Keep Multiple Sclerosis at Bay?

Post by frodo » Fri Dec 21, 2018 6:27 am

Could an Aspirin a Day Keep Multiple Sclerosis at Bay?

http://www.alsresearchforum.org/could-a ... is-at-bay/

People take aspirin for pain, fever, and even in hopes of warding off a heart attack. Could this old, over-the-counter pill also help control multiple sclerosis? A November 27 report in Science Signaling suggests as much—in mice. Scientists led by Kalipada Pahan, Jesse Brown Veterans Affairs Medical Center in Chicago, claim that a small, daily dose of aspirin suppressed inflammation, demyelination, and autoimmune responses in mice modeling MS. It worked by restoring regulatory T lymphocytes (Tregs), which rein in self-reactive T cells.


Protect and serve? A low-dose aspirin regimen reduced MS symptoms in MS model mice by restoring regulatory T cell levels. [Image: Regulatory T cells in multiple sclerosis and myasthenia gravis. Courtesy of Danikowski et al., 2017. CC BY 4.0].

Given that Tregs also dwindle in amyotrophic lateral sclerosis, the new data beg the question of whether aspirin could benefit ALS patients. “In both MS and ALS, the number and function of Tregs decrease, resulting in aberrant immune responses and increased inflammation,” Pahan wrote to Alzforum, “It has been already shown that infusion of Tregs slows the progression of ALS, so there is a possibility that low-dose aspirin may delay the progression of ALS via boosting Tregs.”

However, Pahan cautioned that long-term use of even baby aspirin (81 mg/day) may cause stomach upset and heartburn. Bradley Turner, University of Melbourne, Australia, also urged caution, noting there is little evidence of a connection between aspirin and ALS. “It is unclear whether the same mechanisms are operating in ALS and its animal models. However, this would be an interesting future line of inquiry,” Turner wrote to Alzforum.

Experimental autoimmune encephalitis (EAE), a commonly used model for MS in mice, is an inflammatory demyelinating disease of the central nervous system that is clinically and pathologically similar to MS. First author Susanta Mondal and colleagues induced relapsing-remitting or chronic EAE in five-week-old wild-type mice. Eight days later, the scientists started giving the mice 1 to 3 mg/kg aspirin a day by oral gavage for up to 32 days.

Even at the lowest dose, aspirin halved the clinical scores of both models, reducing limb and tail weakness, paralysis, and death compared with untreated EAE mice. In treated mice, fewer peripheral immune cells infiltrated the spinal cord, expression of pro-inflammatory mediators was lower, and axons in the spinal cord had more myelin. Aspirin seemed to work by preventing an EAE-induced loss of regulatory T cells by increasing the expression of interleukin-11, an immunomodulatory cytokine with anti-autoimmune activity. This prevented development of pro-inflammatory T helper 17 cells, Mondal and colleagues reported.

The results suggest that aspirin could potentially slow progression in people with ongoing disease, Pahan wrote. He plans to next conduct clinical trials of aspirin treatment in patients with MS.

Unlike MS, ALS is not considered primarily an autoimmune disorder. Yet its motoneuron degeneration is accompanied by marked neuroinflammation involving both brain-resident glia and invading monocytes and T cells. Tregs have been reported to become both depleted and dysfunctional in ALS, particularly in people with rapidly progressing disease (Beers et al., 2017).

Some evidence suggests that boosting the number of Tregs could slow ALS progression (see June 2018 news). One experimental attempt involves autologous cell treatment. In mice, this delays progression (Sheean et al., 2018; for review, see Thonhoff et al., 2018). In an open-label pilot study of three patients, led by Stanley Appel and Jason Thonhoff of Houston Methodist, ex-vivo expansion and reinjection of a patient’s own Tregs delayed progression of their ALS (Thonhoff et al., 2018).

Could aspirin shore up the supply of neuroprotective Tregs in ALS? It’s unclear, Turner told Alzforum. Prospective cohort studies found no link between aspirin use and risk for ALS (Fondell et al., 2012). One large population-based, case-control study did suggest aspirin reduced risk, but that finding has yet to be replicated (Tsai et al., 2015). Another study suggested aspirin delayed disease onset in SOD1 G93A mice; however, the doses used were 100 times higher than in the current study, so may not hold at low doses (Barnéoud and Curet, 1999).

“The authors have made an interesting observation linking aspirin, IL-11, and Tregs in EAE mice. Whether this mechanism occurs in humans and ALS is unclear from the paper,” Turner wrote. “Therefore, there is no hard evidence to suggest that people with ALS should be taking aspirin.”

“I would hesitate to extrapolate that much from an animal model,” Thonhoff agreed. However, given that aspirin is inexpensive and available, it would be relatively easy to test it in small pilot trials for MS and ALS patients, he said. If a signal emerges, a larger study would be in order. “We think any treatment that can enhance the Treg population, or prevent the loss of the immunosuppressive functions of Tregs, has a chance to slow down the progression of ALS,” Thonhoff added. However, given the potential side effects and lack of evidence for benefit in people, Thonhoff does not recommend the daily use of aspirin in ALS patients at this time.

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Re: Could an Aspirin a Day Keep Multiple Sclerosis at Bay?

Post by hpmmd » Mon Dec 24, 2018 12:28 am

It is interesting that this would be suggested. I can report on a series of one patient.

I am a physician, who in 2005 was forced to retire following the onset and progression of MS. In 1974, while still in Medical School, I concluded that a daily dose of aspirin might be of value for the prophylaxis for several diseases. From that time on (43 years) I took and continue to take a daily enteric aspirin dose of between 162 and 325 mg.

I can only report that in my case, there was no protective effect against MS, though I believe it has been beneficial against the diseases for which I have been taking it.

The optimists might say that I should think of how much earlier my symptoms might have begun or how much worse they might have been.

HPM, M.D.

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Re: Could an Aspirin a Day Keep Multiple Sclerosis at Bay?

Post by eastcoastsoxfan » Thu Jan 17, 2019 6:09 pm

I went to Poland 8 years ago, had my veins opened.
When I returned I threw what MS drugs I had in the garbage and after my blood thinners ran out I started taking an aspirin a day.
I've always exercised regularly(hiking, hunting, working outdoors) and have always felt great since the procedure, however during the past couple of years I've changed my diet(almost no dairy,salt, fried, etc) and feel even better, I'm 44 and am just as active as when I was 25.
Not saying it's because of the daily aspirin but I'm betting it didn't hurt

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