Neuro-protection

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Neuro-protection

Postby bromley » Fri Jul 01, 2005 5:12 am

Dear all.

At the end of May 2005 the UK MS Society held its annual research conference. The focus of the conference was neuro-protection (a recognition that tackling attacks / inflammation alone was not enough. It's still early days but there are signs that some trials are beginning to take place). Fingers crossed that some effective treatments are delivered in the future. One of the ways they will test for effectiveness is to measure if the drugs slow down the shrinkage to our brains (caused by MS)! And they wonder why I don't sleep well at night!

Anyway, it sort of looks promising, but as ever with MS, better treatments are always 'just around the corner'.

http://www.mssociety.org.uk/go.rm?id=14088
http://www.mssociety.org.uk/go.rm?id=14112

Perhaps the future treatment of this curse will involve drugs to reduce attacks / inflammation and drugs to stop nerves being damaged and/or killed. The latter may involve drugs to reduce damage caused by nitric acid / sodium etc etc. I don't mind how many drugs I take as long as they work. What is also needed are drugs to regenerate the damaged and dead nerves, but not sure if this is possible. Anyway, a tiny ray of hope.

Have a good weekend

Bromley
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Postby DenverCO » Fri Jul 01, 2005 10:45 am

Bromley,

Focus absolutely needs to be directed towards neuroprotection. Even if the main problem is inflamation (and I don't necessarity believe that it is), we need to preserve our nervous systems in light of how rapidly MS progresses compared to how long it takes to research/introduce new therapies.

You mentioned that you don't care how many drugs you have to take as long as they work. I had to laugh because I used to be one of the I-don't like-to-put-chemicals-in-my-body people, then once I started injecting myself my attitude changed. I don't care if every cell of my being is marinating in pharmaceutical agents, just as long as they work!
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Postby Arron » Fri Jul 01, 2005 11:31 am

marinating in pharmaceutical agents
... LOL I loved that!
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Re: Neuro-protection

Postby NHE » Sun Jul 03, 2005 3:06 am

Bromley wrote:One of the ways they will test for effectiveness is to measure if the drugs slow down the shrinkage to our brains (caused by MS)! And they wonder why I don't sleep well at night!

Brain atrophy and MS has been studied for a while now. A Pubmed search for <"multiple sclerosis" AND atrophy> brings up many interesting papers. Moreover, I remember reading one a few years ago that compared atrophy and axonal transection in control subjects vs. those on Avonex. The results were that at the one year time point atrophy was the same in both groups. However, by the two year time point both atrophy and axonal transection were significantly reduced in the Avonex treated group as compared to the untreated group. Unfortunately, I've been unable to find this precise paper in either my own database or in Pubmed. Hmm, nor could I find it in my file cabinet... I'll keep looking. Anyways, it seems that treatments that slow the progression of disability also slow down the atrophy process. I agree that what's exciting now is that there may be a way to reverse the process to regain function. Perhaps that bright spot at the end of tunnel really isn't a train.

NHE
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Hormones and Neuroprotection

Postby Shayk » Wed Jul 06, 2005 6:55 pm

NHE

I sure hope you find that abstract about Avonex and brain atrophy. I thought I recalled reading something to the effect that a placebo group displayed less brain atrophy after two years on interferons.

Bromley

I appreciate your posting follow-up information from the conference. I definitely think neuroprotection is the future of MS management. You’ve given me a perfect opportunity to post some information about hormones and neuroprotection. :) The information is not specific to MS but I think it illustrates the future potential of hormones to help manage it.


Progesterone (Guys, you have progesterone too, just not quite as much as women.)

Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination

….locally synthesized PROG are likely to play an important role in the viability of neurons and in the formation of myelin sheaths.

Local synthesis of PROG in the brain and the neuroprotective and promyelinating effects of this neurosteroid offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes and for preserving cognitive functions during aging.


Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord

Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection.


Estrogens

The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties

Among the family of steroidal molecules, only estrogens have the capability of preventing neuronal cell death caused by increased oxidative burden.


Neuroprotection by estradiol

Thus, our view of the role of estrogen in neural function must be broadened to include not only its function in neuroendocrine regulation and reproductive behaviors, but also to include a direct protective role in response to degenerative disease or injury. Estrogen may play this protective role through several routes. Key among these are estrogen dependent alterations in cell survival, axonal sprouting, regenerative responses, enhanced synaptic transmission and enhanced neurogenesis.


Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action

An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult


The role of the estrogen in neuroprotection: implications for neurodegenerative diseases

Although data from human studies remains highly controversial, a large body of research findings suggests that this hormone plays a pivotal role in retarding and preventing the formation of neurodegenerative diseases through its receptor.


Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-actived protein kinase pathway

This study demonstrates that activation of either ERalpha or ERbeta can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.


Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons

Using three indicators of neuronal viability and survival, we demonstrated that both the ERalpha selective agonist PPT and the ERbeta selective agonist DPN protected hippocampal neurons against glutamate-induced cell death in a dose-dependent manner,

As ERbeta is highly expressed in the brain and has little or no expression in the breast or uterus, discovery and design of ERbeta selective molecules could provide a strategy for activating the beneficial effects of estrogen in the brain without activating untoward effects of estrogen in reproductive organs.


Guys, I think there is some work already underway to design selective estrogen receptor modulators (SERMS) for MS to eliminate “feminizing” effects of estrogens.

We’re all doing our best to see that bright spot at the end of the tunnel. Take care everyone. I’m marinating my brain in hormones and pharmaceuticals. :)

Sharon
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hormone research reports/thanks

Postby ljm » Thu Jul 07, 2005 8:22 am

Sharon,
May be the wrong thread, but wanted to thank you for this summary of research. I printed out all of them. I found a compounding pharmacy in my town, they are familiar with bio identical hormone preparation, they use a ZRT affliate saliva testing lab in Canada, and were able to provide a GP in area who is familiar with treatment of MS with hormones (apparently...my appointment is next week...) All this was triggered by your posts and pms to me and I think is an avenue at least worthy of exploring. Many thanks again.
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Postby Arron » Thu Jul 07, 2005 3:09 pm

Sharon, our thanks as well (and as always) for being such a wonderful contributor to the community.
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Thanks!

Postby Shayk » Mon Aug 22, 2005 8:39 pm

ljm and Arron—a very belated but very sincere thank you for your comments.

Sharon
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