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Clinical Translation of Stem Cells in Neurodegenerative Disorders
ENV
Posted: Friday, February 03, 2012 1:02:36 AM

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ISSCR: Committee Forum (PDF)


-- Le Meilleur Vin Avec Les Meilleurs Amis --

The comment above is my personal opinion. I do not represent ALS-TDI
ELYSEE RECLUS
Posted: Friday, February 03, 2012 10:16:16 AM

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avoutersterp
Posted: Friday, February 03, 2012 10:34:16 AM
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tx far away


Arthur van Outersterp
dx PLS 1999
ELYSEE RECLUS
Posted: Friday, February 03, 2012 11:10:46 AM

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no, i believe near ten to 15 years for replacement, near 5/7 years for stabilisation (brainstorm and neuralstem ongoing!
De Laval
Posted: Friday, February 03, 2012 11:13:49 AM
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Elysee.
How about your WF10 trial did you already starting
Jan
ELYSEE RECLUS
Posted: Friday, February 03, 2012 11:44:14 AM

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my wf10 IS somewhere between thailand and france. i discovered the german pharmacist wanted to sell it 370€ per vial 4PHARMACY fees, so that i ordered it directly in thailand http://www.oxothai.com/ with a physician prescription send by mail at price of 135€ per vial. I lost one month with this story. but now it is on the road again;
Fafut_1
Posted: Friday, February 03, 2012 3:00:35 PM
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good lecture Env, I read with most interests paragraphs related to ALS. Another paper supporting brainstorm approach and showing stem cells use if far more complicated from simple "cells" injections.

Wonder what is the potential behind combination of NP and brainstorm protocol. Hope there is no "molecular conflict" and both will turn out compatible.
ENV
Posted: Friday, February 03, 2012 4:26:35 PM

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I would guess NP + Brainstorm to be a good fit but I am not a doctor.

-- Le Meilleur Vin Avec Les Meilleurs Amis --

The comment above is my personal opinion. I do not represent ALS-TDI
Fafut_1
Posted: Friday, February 03, 2012 8:12:40 PM
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pity, I guessed u would prescribe me some;)
criscapelo
Posted: Monday, February 06, 2012 6:01:30 PM
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ELYSEE RECLUS wrote:
my wf10 IS somewhere between thailand and france. i discovered the german pharmacist wanted to sell it 370€ per vial 4PHARMACY fees, so that i ordered it directly in thailand http://www.oxothai.com/ with a physician prescription send by mail at price of 135€ per vial. I lost one month with this story. but now it is on the road again;


Our internatinal pharmacy in Germany took 200 € per vial last year. It was in Munich. The problem ordering WF10 directly from Thailand is that it can be retained in the customs. Khuene explained the legal method was importing it via an international pharmacy.

Cristina
Nemesis
Posted: Wednesday, February 08, 2012 9:04:55 AM

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This is an interesting variation of the current theme in the G93A model: Instead of using chlorite to convert M1 macrophages to M2 they are simply using Clodronate liposome to selectively kill all activated macrophages, thereafter replacing them by transplanting wild-type bone marrow cells (i.e. progenitors to novel macrophages).


Biochem Biophys Res Commun. 2012 Jan 17. [Epub ahead of print]
Replacement of microglial cells using Clodronate liposome and bone marrow transplantation in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.
Lee JC, Seong J, Kim SH, Lee SJ, Cho YJ, An J, Nam DH, Joo KM, Cha CI.

Abstract
Disease progression of amyotrophic lateral sclerosis (ALS) is partially mediated by the toxic microenvironment established by microglia. In the present study, we used SOD1G93A transgenic mice as an in vivo ALS model and replaced microglia expressing mutant SOD1 (mSOD1) with microglia expressing wild-type SOD1 (w/tSOD1) to modulate the toxic microenvironment. Stereotactic injection of Clodronate liposome, a selective toxin against the monocyte/macrophage system, into the fourth ventricle of the brains of 12-week-old asymptomatic ALS mice reduced the number of microglia effectively in the central nervous system. Subsequent bone marrow transplantation (BMT) with bone marrow cells (BMCs) expressing w/tSOD1 and GFP leads to replacement of the endogenous microglia of the ALS mice with microglia expressing w/tSOD1 and GFP. The expression of mSOD1 in the other neural cells was not influenced by the replacement procedures, and immunological side effects were not observed. The replacement of microglia significantly slowed disease progression and prolonged survival of the ALS mice compared with the ALS mice treated by stereotactic injection of PBS-liposome and BMT with BMCs expressing mSOD1 or w/tSOD1. These results suggest that replacement of microglia would improve the neural cell microenvironment, thereby slowing disease progression. The mechanisms and functional implications of this replacement require further elucidation.

PubMed


Don't just ask what scientists can do to speed up the solution for ALS or when they will do it, instead ask yourself what you can do right now to solve ALS asap.
Olly
Posted: Wednesday, February 08, 2012 1:05:01 PM

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Another bone transplanting procedure that shows promise?

CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS.


Department of Neurology, Methodist Neurological Institute, Houston, TX, USA.
Abstract

Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu(2+)/Zn(2+) superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression.

However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known.

Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4+ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters.

Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation.

These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4+ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia.

These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.

PMID:18809917
[PubMed - indexed for MEDLINE]
PMCID: PMC2547419


Incidently NAC( N-acetyl-cysteine)is supposed to partly act by increasing CD4 T Cells production in FALS.

See the thread -
http://www.als.net/forum/yaf_postsm346959_Searching-for-new-substances-for-PALS.aspx#346959

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
ENV
Posted: Wednesday, February 08, 2012 11:40:58 PM

Rank: Administration

Groups: Administration , Member

Joined: 11/21/2007
Posts: 2,259
Location: USA
Nemesis wrote:

This is an interesting variation of the current theme in the G93A model: Instead of using chlorite to convert M1 macrophages to M2 they are simply using Clodronate liposome to selectively kill all activated macrophages, thereafter replacing them by transplanting wild-type bone marrow cells (i.e. progenitors to novel macrophages).


Biochem Biophys Res Commun. 2012 Jan 17. [Epub ahead of print]
Replacement of microglial cells using Clodronate liposome and bone marrow transplantation in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.
Lee JC, Seong J, Kim SH, Lee SJ, Cho YJ, An J, Nam DH, Joo KM, Cha CI.

Abstract
Disease progression of amyotrophic lateral sclerosis (ALS) is partially mediated by the toxic microenvironment established by microglia. In the present study, we used SOD1G93A transgenic mice as an in vivo ALS model and replaced microglia expressing mutant SOD1 (mSOD1) with microglia expressing wild-type SOD1 (w/tSOD1) to modulate the toxic microenvironment. Stereotactic injection of Clodronate liposome, a selective toxin against the monocyte/macrophage system, into the fourth ventricle of the brains of 12-week-old asymptomatic ALS mice reduced the number of microglia effectively in the central nervous system. Subsequent bone marrow transplantation (BMT) with bone marrow cells (BMCs) expressing w/tSOD1 and GFP leads to replacement of the endogenous microglia of the ALS mice with microglia expressing w/tSOD1 and GFP. The expression of mSOD1 in the other neural cells was not influenced by the replacement procedures, and immunological side effects were not observed. The replacement of microglia significantly slowed disease progression and prolonged survival of the ALS mice compared with the ALS mice treated by stereotactic injection of PBS-liposome and BMT with BMCs expressing mSOD1 or w/tSOD1. These results suggest that replacement of microglia would improve the neural cell microenvironment, thereby slowing disease progression. The mechanisms and functional implications of this replacement require further elucidation.

PubMed


Wow. That is some kind of aggressive. It will be a long time in safety trials because wiping out microglia and replacing is quite perilous. Perhaps some of the experience with bone marrow replacement can be instructive. I know there are projects underway to add astrocytic precursors to reset the behavior of endogenous astrocytes. Perhaps a future combo therapy?

-- Le Meilleur Vin Avec Les Meilleurs Amis --

The comment above is my personal opinion. I do not represent ALS-TDI
Olly
Posted: Thursday, February 09, 2012 8:28:06 AM

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Joined: 7/4/2011
Posts: 1,288
Location: United Kingdom
ENV,
I think you're on the right track there as complete replacement would be extremely hazardous.

By that I mean when you said - discovering astrocytic precursors to reset the behaviour of endogenous astrocytes.

That would also mean understanding how and why macrophages and nutrients are defective and the related chemical/electrical mechanisms of defection. I don't think we are anywhere near that stage yet and we are still in the trial and error period.



Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
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