Detailed Minocycline Research info

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Detailed Minocycline Research info

Postby viper498 » Mon Jun 11, 2007 4:41 am

See link below. This points to the Wisconsin Alumni Research Foundation (WARF). The link points to Dr. Ian Duncan's Research, however it is buried in the patent application. I was disappointed that someone has already patented this, because it tells me that profit is the motivator? Right? Anyway, good info, even if it is on rats...

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Postby tory2457 » Mon Jun 11, 2007 5:15 am

profit being a motivator when it comes to sick people? hmmm,

anyway, you're connecting the dots-great! being you're own advocate is a sure fire way of taking control of your recovery.

Here's a great link I have and still read:
http://www.immed.org/

Lots to read and Prof Nicholson talks about Mycoplasma as well.

the best to you Brock,
tory
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Postby SarahLonglands » Mon Jun 11, 2007 5:40 am

Brock, profit isn't always the reason for medical patents. Stratton, Mitchell
and Sriram have a patent for the Vanderbilt work, but it is just to claim intellectual property, not to make money: http://www.freepatentsonline.com/6890526.html

As an optimist, I would like to think it is the same here, but I'm really not sure.

Sarah
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby viper498 » Mon Jun 11, 2007 5:50 am

Sarah,

Thanks for the clarification then. Again, I am being cynical. So many people are trying to profit from these sort of things. I am sure that in this case, it is just to lay claim.... I am all for researchers getting credit and notariety for their discoveries. I'll personally pull out the red carpet for the one (s) that discover the cause of MS.

Brock
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Postby gwa » Mon Jun 11, 2007 6:59 am

tory,

That is a really good link. Thanks for posting it.

gwa
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Postby tory2457 » Tue Jun 12, 2007 5:54 am

gwa,

you're welcome!

I have tons of good links....if you're interested! :D :wink:
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Postby finn » Tue Jun 12, 2007 11:22 pm

This is one of the posts I removed when I got pissed and left the board after a serious disagreement. I think it suits this thread well, so maybe it's worth reposting:

It is not just hype, and it has not come out of nowhere. The research history of minocycline as a neuroprotective agent is a combination of creative thinking, hard work and a bit of luck:

1998 - Minocycline is found to be neuroprotective in an animal model of stroke

In 1998 a group of Finnish researchers finds out that "lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against global ischemia in gerbils". In 1999 group leader Jari Koistinaho states in a major Finnish newspaper that minocycline is effective in preventing disability caused by stroke in an animal model, and it should be tested in a clinical trial. Unfortunately - as far as I know - no such trial has been conducted in Finland yet.

2001 - Minocycline is found to be neuroprotective in a cell culture of ALS

Finnish researcher Tiina Tikka, who worked in the team that studied minocycline in ischemia stroke, also studies minocycline in cell cultures of cerebrospinal fluid from patients with ALS. Her doctoral thesis is based on the positive findings of the study, and is titled "Neuroprotective Effects of Tetracycline Derivates in Primary Cell Culture Models of Excitotoxicity and Inflammation" (abstract is only in Finnish, sorry).

2001 - Minocycline reduces the severity of EAE in mice

A team of American and German researchers lead by Dr Ian Duncan discovers that minocycline can reduce the severity of EAE in mice. Duncan says that his team considered trying minocycline to treat MS because "Finnish studies had shown the antibiotic stopped the activation of microglial cells, which patrol the brain and respond to immune events, in stroke patients".

2001 - First clinical trial of minocycline in MS is to be started in Canada

"The Canadian Institutes of Health Research (CIHR) announced funding of more than $5 million over five years for a study of the role that enzymes called matrix metalloproteinases (MMPs) have in multiple sclerosis. This interdisciplinary study headed by Dr. V. Wee Yong of the University of Calgary will focus on all aspects of MMPs from the environmental, biological and therapeutic aspects and involve researchers at five different universities. Part of the study will be a Phase I clinical trial of the common acne medication minocycline in relapsing-remitting MS." (MS Society of Canada, Medical Update Memo)

"We chose minocycline since it anecdotally appeared to improve the condition of MS patients who were using it for acne relief and later determined the important effect of minocycline as an MMP inhibitor." (MMPs in MS, Canada)

2002 - First clinical trial of minocycline in ALS is conducted in the USA

The trial is conducted at California Pacific Medical Center in San Francisco. Its results show that high doses of minocycline appears to be safe and well tolerated by patients with ALS. The study was not designed to test effectiveness of the drug in ALS. Larger, multicenter study of minocycline for ALS is started in 2003 and is under way.

2003 - Minocycline is now studied in a broad range of neurological disorders

A team of Harvard Medical School researchers states that "minocycline, a semisynthetic tetracycline, has demonstrated remarkably broad neuroprotective properties in experimental models of ischemic stroke, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, multiple sclerosis, and Parkinson's disease".

2003 - Preliminary results of the MS trial are presented at the AAN meeting

"At the AAN meeting, scientists reported on the first clinical trial of minocycline in MS (3). Ten patients with active relapsing-remitting MS were enrolled in the study. After a three-month observation period, treatment was initiated with minocycline by mouth twice daily. Whereas prior to treatment, 80% of patients had active MS by MRI scanning, none of the treated patients have shown subsequent MRI evidence of activity, as much as nine months later. There have been no safety concerns. It is likely that larger MS trials of minocycline will be initiated over the next year." (Veritas Medicine)

2004 - Minocycline is found to produce neuroprotection in MS

Dr V. Wee Yong, who is responsible for the Canadian minocycline trial together with Dr Luanne Metz, suggests in an article "the prospect of an experimental treatment, minocycline, in producing neuroprotection in MS". In the article he also evaluates "the possibility that glatiramer acetate (Copaxone) enables neuroprotection in MS through beneficial inflammation".

2004 - Results of the MS trial are presented in the may issue of Annals of Neurology

Selected quotes from the letter titled "Minocycline Reduces Gadolinium-Enhancing Magnetic Resonance Imaging Lesions in Multiple Sclerosis":

"We report a trial of minocycline in people with relapsingremitting multiple sclerosis (RRMS) that evaluates safety and estimates its effect on magnetic resonance imaging (MRI). Ten subjects with active RRMS received oral minocycline 100mg twice daily for 6 months after a 3-month run-in period. A 30-month treatment extension is ongoing."

"During the trial, there were no serious adverse events or laboratory abnormalities and no change in EDSS."

"There were no active scans after month 2 (Fig) and no new active lesions after month 1. Although five patients accounted for all MRI activity before and after treatment, all patient data were included in all analyses."

"Small sample size and short trial duration limit conclusions, but reduced MRI activity is encouraging and calls for definitive studies to establish minocycline efficacy in MS."
(Annals of Neurology, page 756)

2004 - Minocycline will be tested in a clinical trial together with Copaxone

Teva Pharmaceutics, the manufacturer of Copaxone, is sponsoring the future trial. Maybe the combination therapy will be more effective than either of the drugs alone, but hopefully the researchers get a change to test minocycline also as monotherapy.

Is minocycline a novel way to treat MS?

In my opinion, yes. It has anti-inflammatory properties like all current treatments, but the key issue with minocycline is neuroprotection. According to an Australian study the first sign of new MS attack could be the death of oligodendrocytes (myelin making cells), and it is the programmed cell death that triggers the autoimmune reaction shown as active MRI lesions. It might be possible that during the clinical trial neuroprotective properties of minocycline were even able to lessen the amount of dying oligodendrocytes, which then showed as a lack of new autoimmune reactions and MRI activity in all treated patients.

It won't be a miracle drug, but it might as well be able to protect our body from further damage caused by MS better than any of the current treatments. Unfortunately it probably will take years before we know it for sure.

(originally posted may 2004)

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby bromley » Wed Jun 13, 2007 2:56 am

Finn,

Excellent post.

Minocycline is also being studied by one of the teams funded by the NMSS under its Promise 2010 initiatitve:

Dr. Ian D. Duncan’s Team (University of Wisconsin, Madison)

“We have made some significant progress toward our long-term goal of initiating a clinical trial in MS.”

Experimental models: In the rat, we established a focal model of MS-like EAE in the spinal cord that results in neurologic defects in the hind limbs. We will use this model to explore the anti-inflammatory effects of the antibiotic minocycline, and the restorative capabilities of immature myelin-making cells (oligodendrocyte progenitors) transplanted into, or adjacent to the lesion.

In the “Biozzi” mouse, we have shown a correlation between progressive disability and nerve fiber loss. We can now compare these findings after attempting treatment to protect tissue or after cell transplantation. We also established an EAE model in marmosets and identified disturbance of the visual system of 100% of those with EAE. As one can now putatively evaluate the loss of nerve fibers in the optic nerve using a technique known as ocular coherence tomography (OCT), we have initiated studies using OCT in the marmoset. We believe that this model offers great opportunities to explore neuroprotective therapies.

Repair cells: We isolated oligodendrocytes (myelin-making cells) from stem cells and succeeded in coaxing them to specialize (differentiate) into oligodendrocytes in increasing numbers and percentage using selective growth factors. We have also shown that these cells make myelin when transplanted into animals that are myelin-deficient, thus proving their functional capabilities.

Imaging: We have been evaluating MRI measures to develop a predictive model of central nervous system tissue structure and function (myelin growth, axon preservation, scarring, and inflammation). We developed advanced imaging protocols for improving the information obtained with MRI, diffusion transfer and magnetization transfer measurements.


We have been evaluating a PET (positron emission tomography) imaging tracer which is used to label microglia, cells which are present in regions of active inflammation in the central nervous system. We have significantly improved the synthesis of this tracer to obtain increased specific activity. In addition, a new small animal PET scanner has been installed, enabling the detection of smaller lesions in small animal models.
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Postby viper498 » Wed Jun 13, 2007 4:33 am

Finn,

Great post. The only comment I have is that we don't have 'years' to sort it out. There is some good scientific evidence that Minocycline is effective in treating MS. It definitely seems to do better than any of the DMD's. It would seem to me, given the safety profile of Minocycline, that at this point it could become standard protocol to prescribe this to all CIS patitets as well as RRMS patients. I will probably get better efficacy from the Minocycline than I do Rebif, infact I am almost sure of that. I'll get off my soap box now.

Again thanks for the post!!

Best Regards,
Brock
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Postby viper498 » Wed Jun 13, 2007 4:50 am

Ian,

At this point I am not impressed with the University of Wisconsin Team. They have dragged their feet on this since 2001. They are only saying now that they have made progress toward INITIATING a clinical trial? They should have been well in to a clinical trial by now, especially after the results that their initial research yielded.

I am impressed with Dr. V. Wee Yong, and Dr. Luanne Metz. They have applied this directly to clinical applicability. They didn't waste a lot of time. These are the sort of studies that we really need to see. Hopefully Dr. Metz/Dr. Yong are planning another larger study with a much larger sample size (more participants).

This would tell us whether minocycline can even prevent new relapses or progression. That is the part that will have to be proven by time.

Brock
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Postby viper498 » Wed Jun 13, 2007 5:42 am

WTF!!! I am so confused. See below. This is from the NMSS. Notice where they say "Did not reach statistical significance". Granted, it was in combo with copaxone. I can understand that it may reduce the efficacy of Mino because copaxone is designed to build up the BBB, so maybe it lets less of Mino in??? Still.. Then they also said nothing on the NMSS about the Minocycline Pilot Study results. If they say that has no "Statistical Significance" then I will have lost ALL confidence in the NMSS.

Brock

· Dr. Luanne Metz (University of Calgary, Alberta) and colleagues studied the effects of adding on oral minocycline an antibiotic to Copaxone versus treatment with Copaxone and placebo in 40 people with RR MS. Minocycline has been shown to inhibit proteins that contribute to the immune attack in MS. The primary outcome measured was a reduction in active brain lesions. The results show a trend to improvement in this outcome, as well as in relapse risk but the results did not reach statistical significance. Treatment was safe and well tolerated. The authors note that further study of minocycline is warranted because it is safe and inexpensive. (Abstract #S02.003)
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Postby finn » Wed Jun 13, 2007 11:48 am

viper498 wrote:There is some good scientific evidence that Minocycline is effective in treating MS. It definitely seems to do better than any of the DMD's. It would seem to me, given the safety profile of Minocycline, that at this point it could become standard protocol to prescribe this to all CIS patitets as well as RRMS patients.

Brock, I agree with you, but to officially turn minocycline into a MS drug would require a larger clinical trial where it would be compared against placebo or one of the ABCRs. That would cost money, and nobody seems to be willing to pay for it.

Anyway, thanks for your comment.

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby tory2457 » Wed Jun 13, 2007 11:51 am

Thanks for the post Finn.

Brock,

yeah, good thoughts you're having.
IMO, until they can replace all the drugs etc used with the treatment of MS do you really think they are going to open that Proverbial Can of Worms? Shared Solutions would be ---For What? hmmm, hard to believe that the powers to be are chosing NOT to look in the right direction, but big business baby is the way things work!

btw, do you have low body temperature?
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Postby viper498 » Wed Jun 13, 2007 1:39 pm

Tory,

I don't think I have low body temp. I always feel like I am hot... k

Brock
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Postby Lyon » Wed Jun 13, 2007 1:52 pm

viper498 wrote: I don't think I have low body temp. I always feel like I am hot...
You feel hot to other people or your perception is that you're hot?

Interesting question, my wife always says she is freezing but she produces so much body heat that I have to sleep on top of the blankets or my restless legs could win the Boston Marathon for me while I'm sleeping.

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