now they may be beneficial

Discussion of statins (Lipitor, Zocor, etc.) in the treatment of MS.
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scorpion
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now they may be beneficial

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joge
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Post by joge »

Really, I'm happy reading these results. But..

5 years ago, I started using 80 statine because of a similar trial. More research was nessasary, it ended...

And now, 5 years later.. same test, similar result, small group, so.... more resears is nessasary...

:?

When are the results good enough? Why wait using statines. I don't!
I'm ready, I'm ready !
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jackD
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Re: now they may be beneficial

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J Neuroimmunol. 2007 Mar;184(1-2):17-26. Epub 2007 Jan 10.

Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets.

Aktas O, Waiczies S, Zipp F.
SourceInstitute for Neuroimmunology, Neuroscience Research Center, Charité -- Universitätsmedizin Berlin, Germany.

Abstract
Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS) and the major cause of neurological disability in young adults in Western countries. In spite of intensive research efforts, treatment options established to date do not sufficiently prevent the accumulation of tissue damage and clinical disability in patients with MS. We here describe recently identified molecules responsible for the inflammatory and the neurodegenerative processes in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), and review new treatment options targeting both aspects of this disease.

PMID:17222462

Here is the full text that will tell you what the novel therapeutic targets are.
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http://home.ix.netcom.com/~jdalton/egcg-neorond-ms.pdf

jackD
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CureOrBust
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Post by CureOrBust »

joge wrote:When are the results good enough? Why wait using statines. I don't!
The results that are not good enough are "these drugs are so broadly used throughout the United States and the world, and to learn whether a relatively inexpensive oral therapy".

I have always read the word "inexpensive" to mean no money to be made, and therefore no funding for a trial.
Although, it does make me wonder why no one has looked to duplicate and create a substance that works on the same pathway as say Lipitor, but better; and therefore have a new patentable substance. Or is Lipitor (or whatever statn works for you, I originally tried Simvastatin) as good as it can be? or the modification to small to generate a new patent? :?

I too have been on 80mg Lipitor for a number of years, and it has been my main "DMD" medication (in my mind).

The link above appears to reference statins on the bottom of page 19. It also speaks about other things, not specifically Statins.
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CureOrBust wrote:
joge wrote:When are the results good enough? Why wait using statines. I don't!
The results that are not good enough are "these drugs are so broadly used throughout the United States and the world, and to learn whether a relatively inexpensive oral therapy".

I have always read the word "inexpensive" to mean no money to be made, and therefore no funding for a trial.
Although, it does make me wonder why no one has looked to duplicate and create a substance that works on the same pathway as say Lipitor, but better; and therefore have a new patentable substance. Or is Lipitor (or whatever statn works for you, I originally tried Simvastatin) as good as it can be? or the modification to small to generate a new patent? :?

I too have been on 80mg Lipitor for a number of years, and it has been my main "DMD" medication (in my mind).

The link above appears to reference statins on the bottom of page 19. It also speaks about other things, not specifically Statins.

That other thing they talk about is EGCG (GREEN/WHITE TEA) Flavonoids and the fact that there seems to be a synergy between them.

I MUST state AGAIN AGAIN AGAIN that ZOCOR(simvastatin) seems to be VERY superior to the other statins in protecting neurons.

jackD

p.s/. 80 mg of Lipitor is deadly and only 80 mg of Zocor is worse!!!

p.p.s. ONLY Zocor(simvastatin) seems to get through the Blood Brain Barrier. Of course there is a possiblility that the MMP-9s may have made holes big enough is some MS folks for the other Statins to enter the brain.

http://home.ix.netcom.com/~jdalton/Yongrev.pdf

J Alzheimers Dis. 2011;23(2):307-18.

Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death.Sierra S, Ramos MC, Molina P, Esteo C, Vázquez JA, Burgos JS.

SourceBioPharma Division, Neuron BPh, Parque Tecnológico de Ciencias de la Salud, Edificio BIC, Armilla, Granada, Spain.

Abstract
There is growing evidence to support the hypothesis that statins may act as neuroprotectants in several neuropathological conditions, including Alzheimer's disease. The mechanisms for neuroprotection are only partially understood, however, and pleiotropic phenomena could be involved.

We have made a comparative study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin), analyzing several parameters that could be related to neuroprotection, such as chemical structure, lipophilicity, potential blood-brain-barrier penetration (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol modulation in neurons, glia, and human hepatocyte cell lines, and protection against neurodegeneration caused by tau hyperphosphorylation induced by okadaic acid.

Our results indicate that monacolin J derivatives (natural and semi-synthetic statins) are the best candidates for the prevention of neurodegenerative conditions due to their higher potential BBB penetration capacity, cholesterol lowering effect on neurons with a satisfactory safety profile, and in vitro protection against cell death caused by okadaic acid in culture.

Among the nine statins studied, simvastatin presented the best characteristics for preventing neurodegenerative conditions.

PMID:21098985
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BMC Med. 2007 Jul 19;5:20.
Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease.

Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE.
SourceBoston University School of Medicine, Boston, MA, USA. bwolozin@bu.edu

Abstract
BACKGROUND: Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.

METHODS:

We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects.

The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.

RESULTS: We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects > or =65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700,000 subjects taking simvastatin and over 50,000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44-0.48, p < 0.0001) and 0.91 (CI 0.80-1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4-0.55, p < 0.0001).

CONCLUSION: Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.

PMID:17640385[PubMed - indexed for MEDLINE]
Last edited by jackD on Tue Apr 08, 2014 3:40 pm, edited 2 times in total.
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Re: now they may be beneficial

Post by CureOrBust »

I first started with Simvastatin for about 6 months, many years ago. There were then a few studies that found Lipitor to be better, So I thought I would try switching. At the time, Simvastatin was appearing to be beneficial, so I was really scared of switching to Lipitor. However, a few hours after the first dose, I personally noticed a slight improvement in tingling in my feet. And other small improvements in the following weeks. At this stage, it is a personal choice by personal experience of what worked better for ME.

As for the "toxicity" of Lipitor, one of the other side benefits of Lipitor, is that it is not as sensitive to the time of day it has to be taken, as opposed to the others which are best taken at night (at least for cholesterol control). Because of this, I actually take the 80mg as two smaller divided doses of 40mg, thereby I hope to have a lower peak serum level at any one time. On my regular blood tests, my liver numbers are all within normal ranges and the indicator for muscle damage are also OK. So, so far so good.

Regarding its ability to cross the BBB, the original papers I read regarding statins lead me to believe that researches thought that their mode of action was actually in their ability to modulate (ie decrease) the permeability of the BBB, so actually measuring the content of spinal fluid for statins would not necessarily align to their effectiveness. Thanks for your concern.
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Re: now they may be beneficial

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How about this study?

Results from a Phase II clinical trial observing possible treatment for progressive MS

MS Update
March 26, 2014
Background:
Currently available therapies for multiple sclerosis are designed to target inflammation. This feature enables them to reduce the frequency relapses, which occur when waves of immune cells enter the central nervous system and cause damage to the protective myelin sheathe. Although successful in treating relapsing forms of MS, this expanding list of therapies remain ineffective for progressive MS. The need for disease-modifying therapies for progressive MS is one that is recognized by the global MS scientific community, who have responded by launching research studies and clinical trials that will hopefully provide clearer answers about this advanced form of the disease.
This month a research team from the UK published a phase II clinical trial exploring the safety and efficacy (ability to produce a beneficial effect) of a cholesterol-lowering drug called simvastatin in people with secondary progressive MS. Statins are widely used in many countries to reduce the amount of ‘bad cholesterol’ produced in the body and lower risk of heart disease and stroke. Emerging research shows that statins can reduce inflammation and block immune cells from travelling into the central nervous system in mice. These abilities pose statins as an attractive candidate for treating MS.
The Study:
Dr. Jeremy Chataway and colleagues from the University College London undertook a 2-year, phase II clinical trial involving 140 volunteers with secondary progressive MS across three neuroscience centres in the UK. They treated 70 people with high dose simvastatin (80mg/day), and the other 70 were given an inactive version of the drug called a ‘placebo’. The type of treatment administered was decided at random. The trial was blinded, meaning the person receiving treatment, the doctor giving the treatment, and the person analyzing the data were all unaware of who received simvastatin and who received a placebo. This is done to avoid bias in the results. The participants were observed over two years. Researchers looked at whether simvastatin had an effect on brain volume loss, known as ‘atrophy’, disability, and the immune system.
Results:
In the group of people with secondary progressive MS who were treated with simvastatin, there was a 43% reduction in the rate of atrophy in comparison to the group who received placebo. Researchers also found that the simvastatin group showed slower changes in EDSS and improved scores on the MSIS-29, a measure of the extent to which MS affects daily life. There was no different between groups in the Multiple Sclerosis Functional Composite (MSFC) score, which measures mobility, dexterity and cognition. The study also showed no differences between groups in levels of inflammation-associated molecules. The occurrence of serious adverse events was similar between groups, and simvastatin was well tolerated with no safety concerns.
Comment:
Overall the results of the clinical trial demonstrate that simvastatin is safe and has a beneficial effect on brain atrophy and disability in people with secondary progressive MS. These results are encouraging and warrant phase III trials to determine the safety and efficacy of simvastatin on a larger group of people with MS as well as when taken over a longer term.
This study is another example of drug repurposing, a process in which a commercially available drug is evaluated for the treatment of a different condition. Drug repurposing is helpful in finding new treatment approaches, especially when time and resources are limited. With very little known about progressive MS, and no treatments available, researchers continue to look at current medications that may have nerve protective or repairing qualities. Click here to read more about drug repurposing and progressive MS.
Source:
Chataway J et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. The Lancet 2014 Mar 19 [Epub ahead of print].
Disponible en français.National Research and Programs

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Re: now they may be beneficial

Post by lyndacarol »

On the negative side, statins interfere with the absorption of vitamin B12, contributing to possible B12 deficiency.
My hypothesis: excess insulin (hyperinsulinemia) plays a major role in MS, as developed in my initial post: http://www.thisisms.com/forum/general-discussion-f1/topic1878.html "Insulin – Could This Be the Key?"
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