Neuro-protection

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Neuro-protection

Postby bromley » Wed Dec 14, 2005 8:28 am

If there was a Father Christmas (Santa Claus to Americans) I would ask for some neuro-protection.

A report has been published about neuro-protection. I haven't got the report but the following article provides a summary of the key points. Hopefully, some of the drugs being examined will come good.

Ian

http://c.moreover.com/click/here.pl?j438161024&w=464753
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Postby Brownsfan » Wed Dec 14, 2005 9:42 am

How about copaxone? Only a small study, but at least it's something....


Copaxone (Glatiramer Acetate) Demonstrated Protection Against Neuronal Injury In Relapsing-Remitting Multiple Sclerosis
KANSAS CITY, MO -- November 14, 2005 -- Clinical research data published in the December issue of Multiple Sclerosis provided evidence that Copaxone® (glatiramer acetate injection) may offer protection from axonal injury and induced neuronal metabolic recovery in patients with relapsing-remitting multiple sclerosis (RRMS).

In a pilot study of 18 RRMS patients using brain imaging techniques, Copaxone was found to produce significant increases in n-acetylaspartate/creatine (NAA/Cr) ratio, an indicator of neuron and axon integrity, compared to four untreated control patients after one year of treatment. This increase was maintained at two years of follow-up.

Additionally, patients treated with Copaxone showed a significant 50% reduction in relapses compared to baseline (p<0.001) while relapse rate in the untreated group remained unchanged.

"The increases in NAA/Cr ratios with Copaxone suggested sustained beneficial effects on cerebral axonal recovery. We believe this indicates a potential for improved electrical conduction pathways in the brain, supporting the emerging concept that, centrally, Copaxone may be acting as a neuroprotective agent," said Omar Khan, MD, associate professor of neurology and director of experimental therapeutics/clinical research, Multiple Sclerosis Center, Wayne State University. "This data is of critical significance because axonal transection is a well-known feature of active MS lesions and represents an irreversible stage of the disease process," said Dr. Khan.

Copaxone Demonstrated Protection/Page Two
Twenty-two treatment-naïve RRMS patients were included in the study. Baseline neurological assessments and magnetic resonance spectroscopy imaging (MRSI) scans were performed. Eighteen patients were treated with Copaxone (glatiramer acetate injection) and followed for 2 years with neurological assessments every six months and MRSI scans annually.

Due to needle phobia, four patients elected to remain untreated and were followed using the same assessment and MRSI schedule. NAA/Cr ratio measurements were obtained in a selected volume of interest (VOI) within the brain and included normal-appearing white matter (NAWM) within the VOI.

In the Copaxone group, the NAA/Cr levels within the VOI were significantly increased by 9.1% at year one and by 10.7% at year two, compared to baseline (P =.03 for both assessments). Conversely, in the untreated group, a 5.5% decrease in NAA/Cr levels was observed in the VOI at year one (P =.04) and an 8.9% decrease at year two (P =.03).

Copaxone patients also demonstrated a 5.4% and 7.1% increase in NAA/Cr ratios within the NAWM at years one and two, respectively (P =.04 for both). Untreated patients had a two% (P = NS.) and 8.2% (P =.03) decrease in NAA/Cr ratios within the NAWM at year 1 and 2, respectively.

"We recognize our study contains limitations, such as the number of patients,
open-label design, and the MRS technique of evaluating NAA levels," stated Dr. Khan. "However, our recently presented three-year data showed sustained improvements in NAA/Cr ratios which clearly demonstrated a long-term clinical benefit and showed that Copaxone treatment may lead to neuronal recovery," said Dr. Khan.

About Copaxone
Current data suggest Copaxone (glatiramer acetate injection) is a selective MHC class II modulator. Copaxone is indicated for the reduction of the frequency of relapses in relapsing-remitting multiple sclerosis. The most common side effects of Copaxone are redness, pain, swelling, itching, or a lump at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

Copaxone is now approved in 44 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all European countries. In Europe, Copaxone is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, Copaxone is marketed by Teva Neuroscience.


SOURCE: Teva Neuroscience
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Postby Jaded » Wed Dec 14, 2005 10:48 am

Brownsfan - your report quoted:

"We recognize our study contains limitations, such as the number of patients"



The minimum accepted number for a trial is 25, if I remember my stats.

However I have heard this quoted before about Copaxone - hopefully there has been more than one study?

If the neuroprotection market is to explode by 2010, that's great. What encouragement is there for continued research for the cause and hopefully a solution that offers remyelination?

They'll be after the fast bucks!

J.
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Postby bromley » Wed Dec 14, 2005 12:49 pm

J,

Organisations such as the Accelerated Cure Project will continue to look for a cause and other organisations are looking at re-myelination. Stem cells also offer potential for replacing lost CNS cells.

But more and more evidence suggests that MS is much more than a disease of de-myelination. There is global damage in the white matter and the grey matter. It is the damage to axons and neurones that causes physical and mental disability. The cause is important, but what if the cause is something which we can't do anything about e.g. genetic susceptibility triggered by a common virus etc. The key thing is to protect what we have left, stem cells or some other mechanism may in the future replace what we have lost.

A breakthrough in neuro-protective agents would help with a huge range of neurological disorders. For the first time, neuros could say 'sorry Mr Bloggs you have a degenerative brain disease, but take one of these neuro-protective tablets a day and it won't progress any further'.

These are just my off the wall thoughts and I might be completely wrong. MS to me is like a lunatic with a machine gun. The bullets are being sprayed all over the place and causing us damage. We have tried to stop the source of the bullets, but without much success. Putting on a kevlar bullet proof vest to protect ourselves seems a sensible strategy until something better comes along to take out the gunman causing the problem in the first place.

Ian
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Postby Jaded » Wed Dec 14, 2005 2:15 pm

Ian

I do agree with you - you are right that it's important to be able to halt progression. And if the stem cells theory works then damage could potentially be repaired. Thanks for putting me straight.


I was having a bad day - sorry Brownsfan. :( So we have at least one neuroprotecive drug....

I'll have plenty of questions when I see my neuro, which reminds me, how did I end up with one who freely admits I know more about current MS reserach than he does??

J.
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Postby Brownsfan » Wed Dec 14, 2005 4:23 pm

Ian, to your knowledge have anti-virals ever been tested on MS? What about the cocktail they give HIV patients?
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Postby dignan » Wed Dec 14, 2005 5:03 pm

I'd like to start by saying I'm not Bromley but in today's episode, the part of Bromley will be played by Dignan...or at least I'm gonna pretend...

Here are a couple of studies from Pubmed relating to HHV6 and EBV and the anti-viral valacyclovir.



Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity.

Acta Neurol Scand. 2005 Dec;112(6):395-402.
Hollsberg P, Kusk M, Bech E, Hansen HJ, Jakobsen J, Haahr S.
Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.

Objective - To assess the presence of Epstein-Barr virus (EBV) and human herpesvirus 6B (HHV-6B) DNA in saliva and plasma from multiple sclerosis (MS) patients enrolled in a randomized, double-blind, placebo-controlled valacyclovir treatment study.

Methods - DNA was prepared following ultracentrifugation of saliva and plasma. EBV and HHV-6B DNAs were determined by real-time polymerase chain reaction.

Results - EBV and HHV-6B DNAs were detected in 41% and 65% of saliva samples, respectively. In patients treated with valacyclovir, the percentage of saliva samples with EBV was significantly reduced (9%; P = 0.000017), whereas the frequency of HHV-6B positive samples was unchanged (57%; P = 0.38 ). Longitudinal studies demonstrated a time-dependent reduction in the frequency of saliva samples containing EBV following valacyclovir treatment. In contrast, plasma contained EBV and HHV-6B DNAs in 17% and 25% of the samples, respectively, and these numbers were not significantly reduced following valacylovir treatment (13% and 16%, respectively), nor were they different from those of healthy controls (6% and 39%, respectively). Patients with high disease activity had a significantly higher frequency of EBV (P = 0.018) and HHV-6B (P = 0.023) positive samples than did patients with low disease activity. The presence of EBV and HHV-6B was strongly correlated in plasma (P < 0.00000001), but not in saliva (P = 0.41).

Conclusion - MS patients express EBV and HHV-6B in both saliva and plasma, but only the expression of EBV in saliva is significantly reduced following valacyclovir treatment. Although EBV and HHV-6B DNAs can be detected in plasma from healthy individuals, the co-expression of both these viruses in MS patients is highly significant and further associated with clinical activity. The observations of viral DNA in plasma are consistent with an underlying immunologic defect in MS.

<shortened url>



A randomized clinical trial of valacyclovir in multiple sclerosis.

Mult Scler. 2005 Jun;11(3):286-95.
Friedman JE, Zabriskie JB, Plank C, Ablashi D, Whitman J, Shahan B, Edgell R, Shieh M, Rapalino O, Zimmerman R, Sheng D.
Department of Neurology, New York University School of Medicine, NY, NY 10010, USA. jef4@med.nyu.edu

OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).

DESIGN/METHODS: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.

RESULTS: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.

CONCLUSIONS: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.

<shortened url>
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Postby bromley » Thu Dec 15, 2005 3:07 am

Brownsfan,

Dignan has picked up on two studies with anti-virals.

If a virus/viruses is/are to blame, the issue to be resolved is what role does it play. It may be that the virus lays dormant and reactivates setting off the immune systems etc. Getting rid of the virus from our CNS would, in this circumstance, be the aim. However, it might be that you get the virus and this corrupts your immune system, which then leads to the cascade of events called MS (inflammation, de-myelination, slow death of axons / neurones etc). But you're right about HIV, they keep this virus in check with the current drugs. This may be the future of MS treatment if a virus is the cause (together with neuro-protective drugs).

Ian
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Postby raven » Thu Dec 15, 2005 10:58 am

The beta interferons were originally developed as anti-virals and were tested against HIV. I guess someone along the line found that they weren't that effective against HIV and decided to give the poor MS mouse a shot instead.

If the immune system has been sensitised to MBP by a pathogen then getting rid of the pathogen won't help that much. You will need to de-sensitise the system.

Robin
Do not go gentle into that good night. Rage, rage against the dying of the light.
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