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Ask the expert

Postby bromley » Sun May 21, 2006 6:50 am

The Canadian MS Society website has added a useful ask the expert section.


Ian

http://www.msanswers.ca/?L=2
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Postby bromley » Sun May 21, 2006 9:52 am

Dear all,

The question that caught my eye was about brain atrophy. At last the experts recognise that more is destroyed than myelin. Several neuro-protective agents are said to be in the pipeline, but surely there's a case for speeding up the research in this area and the testing of drugs. Perhaps they should have list of those who are prepared to be guinea pigs to test these pipeline treatments. Otherwise, if the usual trials process is followed, it could taken another 8-10 years to get something to market. This would be expecially the case with rapidly progressing MS resulting in substantial disability. I'm not sure how they trial drugs for ALS, but given that most patients only survive for five years, patients would be prepared to take the risk given the outcome.

Ian

Q :

I heard that more than just myelin is destroyed in the brain by MS and that the brain actually shrinks. Is that true and is any research taking place to try and stop it?

A :

Yes, the brain actually shrinks in MS. This is due to continuing degeneration (neuro-degeneration) of constituents within the brain as the disease progresses. These constituents include not only myelin and the oligodendrocytes that make myelin in the first place, but also nerve cells (neurons) and their fibers. The shrinkage of the brain, referred to as “brain atrophy”, can be detected by MRI scans of the brain when conducted over periods of years. At autopsy, the loss of brain tissue can be quite obvious to the naked eye.

Neuro-degeneration and brain atrophy are the major factors that account for the progress of disability in patients with MS that deteriorate neurologically. It is thus critical to prevent neuro-degeneration and brain atrophy in MS. Scientists worldwide are actively researching on the reasons for neuro-degeneration and they are beginning to understand some of the molecules that cause this. As a result, a number of medications are being tested in animal models of MS in attempts to prevent the loss of brain tissue. There are indeed many “neuro-protective agents” that seem promising in laboratory studies. Providing for neuro-protection is in fact one of the most active areas of research in MS currently.

There is evidence that the two major types of immunomodulators used in MS, glatiramer acetate (Copaxone) and interferon-betas (Avonex, Rebif and Betaseron), not only affect the immune system but that they also can confer some degree of neuro-protection. The mechanisms by which these immunomodulators provide for neuro-protection seem different, with glatiramer acetate’s action being more direct within the brain tissue, while that of the interferon-betas may be considered more indirect by preventing the entry of molecules that go into the brain to destroy that structure. Many neurologists therefore advocate the use of these immunomodulators in relapsing-remitting MS and to encourage patients to stay on their medications.

We currently have no clear evidence that the loss of brain tissue in progressive MS can be reduced. However, research is quite active in this area.

Overall, we now recognize that neuro-degeneration is very significant in MS, leading to the loss of brain tissue. Research to stop this is very active and several potential neuro- protective medications are in the pipeline.
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cheap neuroprotective agents available now

Postby jimmylegs » Sun May 21, 2006 12:15 pm

http://en.wikipedia.org/wiki/Excitotoxicity

Neuroreport. 2004 Oct 5;15(14):2241-4.
Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity
<shortened url>

Lin Y, Desbois A, Jiang S, Hou ST.

Department of Clinical Neurological Sciences, The No. 252 Hospital of P.L.A., No. 81, Huayuan Street, Baoding City, Hebei Province, China, 071000.

The role of B group vitamins in preventing neuronal death against excitotoxicity was investigated. Neuronal death of cultured mouse cerebellar granule neurons (CGNs) caused by glutamate (50 microM) or NMDA (200 microM) was delayed in CGNs that had been treated with riboflavin (B2), folic acid (B9) or cynocobalamin (B12) for 18 h. Such neuroprotection by B2, B9 and B12 was in a dose- and time-dependent manner. In contrast, application of thiamin (B1), nicotinamide (B3), d-pantothenic acid (B5), pyridoxine (B6) or carnitine (BT) did not ameliorate glutamate or NMDA-mediated excitotoxicity to CGCs. These results are the first indication that certain B group vitamins are not only required for the normal brain function, but can also play a protective role against excitotoxicity to the brain.

J Neurosci. 2001 Jan 1;21(1):98-108.

Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons.
<shortened url>

Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NM.

Departments of Pharmacology and Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.

Although vitamin D hormone (VDH; 1,25-dihydroxyvitamin D(3)), the active metabolite of vitamin D, is the major Ca(2+)-regulatory steroid hormone in the periphery, it is not known whether it also modulates Ca(2+) homeostasis in brain neurons. Recently, chronic treatment with VDH was reported to protect brain neurons in both aging and animal models of stroke. However, it is unclear whether those actions were attributable to direct effects on brain cells or indirect effects mediated via peripheral pathways. VDH modulates L-type voltage-sensitive Ca(2+) channels (L-VSCCs) in peripheral tissues, and an increase in L-VSCCs appears linked to both brain aging and neuronal vulnerability. Therefore, we tested the hypothesis that VDH has direct neuroprotective actions and, in parallel, targets L-VSCCs in hippocampal neurons. Primary rat hippocampal cultures, treated for several days with VDH, exhibited a U-shaped concentration-response curve for neuroprotection against excitotoxic insults: lower concentrations of VDH (1-100 nm) were protective, but higher, nonphysiological concentrations (500-1000 nm) were not. Parallel studies using patch-clamp techniques found a similar U-shaped curve in which L-VSCC current was reduced at lower VDH concentrations and increased at higher (500 nm) concentrations. Real-time PCR studies demonstrated that VDH monotonically downregulated mRNA expression for the alpha(1C) and alpha(1D) pore-forming subunits of L-VSCCs. However, 500 nm VDH also nonspecifically reduced a range of other mRNA species. Thus, these studies provide the first evidence of (1) direct neuroprotective actions of VDH at relatively low concentrations, and (2) selective downregulation of L-VSCC expression in brain neurons at the same, lower concentrations.
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Postby JFH » Sun May 21, 2006 12:26 pm

The problem I have with this site and with this one Expert MS Patient http://www.expertmspatient.com/?spg=PPC is that the "experts" are all medics or medical associates. :x They're all about these professionals beneavolently and patronisingly letting us into a few of their trade secrets. Dont get me wrong I'm all for the provision of academic, research and medical excellence but the real experts are those of us who experience the disease and those who care for us day-to-day. As a minimum the answers must come from a partnership of "them" and "us". IMHO there's a good crop of experts here at TiMS :wink:
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