MaxiScience
2009-02-05
États-Unis - Un essai clinique mené par une équipe de l’université de Chicago montre que l'état des malades atteints de sclérose en plaques s'améliore après une autogreffe de cellules souches.
Vingt-et-un malades ont été transplantés avec leurs propres cellules souches extraites de leur moelle osseuse, après destruction de la moelle par immunosuppresseurs. Le système immunitaire est ainsi « remis à zéro ». Trois ans après cette transplantation, tous les malades n’ont pas connu d’aggravation de la maladie et dix-sept ont vu leur handicap réduire.
La sclérose en plaques est une affection neurologique grave qui pousse le système immunitaire à attaquer la myéline, couche protectrice des fibres nerveuses. Les inflammations sont constatées au niveau du cerveau, dans la moelle épinière et les nerfs. La sclérose en plaques évolue par poussées qui laissent des séquelles lourdes comme des troubles moteurs, des troubles de la coordination, des vertiges ou des problèmes de vue.
Aux différents stades de la maladie, des solutions chimiques existent. Cet essai a été réalisé sur des personnes trentenaires au premier stade de la maladie. Cette technique lourde de traitement ne sera pas applicable à tous les malades.
jeudi 5 février 2009
La vitamine D pourrait prévenir la sclérose en plaques
PsychoMédia
05 février 2009
Une interaction directe entre la vitamine D et une variation génétique associée à la sclérose en plaques (SEP) modifie le risque de développer la maladie selon une récente étude publiée dans PLoS Genetics. L'étude suggère qu'une carence en vitamine D pendant la grossesse et durant les premières années pourrait augmenter le risque de développer la SEP plus tard dans la vie, considèrent les chercheurs.
La SEP est l'affection neurologique la plus fréquente chez les jeunes adules. Des facteurs génétiques et environnementaux sont à l'origine de la maladie.
Des études précédentes avaient montré que les populations des pays de l'Europe du Nord ont un risque plus élevé de SEP s'ils habitent dans des régions moins ensoleillées. Ce qui suggère un lien direct entre une carence en vitamine D, qui est produite par l'organisme en réponse à l'action de la lumière du soleil sur la peau, et un risque accru de SEP.
Le facteur génétique qui est de loin le plus important est la variation DRB1*1501, située sur le chromosome 6, et les séquences ADN adjacentes.
Des chercheurs de l'Université d'Oxford et de l'Université Columbia ont montré que des protéines activées par la vitamine D se lient à une séquence particulière de l'ADN qui se situe près de la variation DRB1*1501 et activent le gène.
"Chez les personnes qui portent la variation DRB1 associée à la sclérose en plaques, il semble que la vitamine D puisse joue un rôle critique", dit Dr Julian Knight, coauteur. "Si trop peu de vitamine est disponible, il est possible que le gène ne puisse pas fonctionner correctement". Ce gène agit sur le système immunitaire (rappelons que la SEP est une maladie auto-immune).
Cette étude suggère que de prendre des compléments de vitamine D durant la grossesse et durant les premières années pourrait réduire le risque de développer la SEP plus tard dans la vie", selon Dr Sreeram Ramagopalan qui a dirigé la recherche. (Il est difficile de combler les besoins en vitamine D par l'alimentation).
Psychomédia avec source:
Science Daily
05 février 2009
Une interaction directe entre la vitamine D et une variation génétique associée à la sclérose en plaques (SEP) modifie le risque de développer la maladie selon une récente étude publiée dans PLoS Genetics. L'étude suggère qu'une carence en vitamine D pendant la grossesse et durant les premières années pourrait augmenter le risque de développer la SEP plus tard dans la vie, considèrent les chercheurs.
La SEP est l'affection neurologique la plus fréquente chez les jeunes adules. Des facteurs génétiques et environnementaux sont à l'origine de la maladie.
Des études précédentes avaient montré que les populations des pays de l'Europe du Nord ont un risque plus élevé de SEP s'ils habitent dans des régions moins ensoleillées. Ce qui suggère un lien direct entre une carence en vitamine D, qui est produite par l'organisme en réponse à l'action de la lumière du soleil sur la peau, et un risque accru de SEP.
Le facteur génétique qui est de loin le plus important est la variation DRB1*1501, située sur le chromosome 6, et les séquences ADN adjacentes.
Des chercheurs de l'Université d'Oxford et de l'Université Columbia ont montré que des protéines activées par la vitamine D se lient à une séquence particulière de l'ADN qui se situe près de la variation DRB1*1501 et activent le gène.
"Chez les personnes qui portent la variation DRB1 associée à la sclérose en plaques, il semble que la vitamine D puisse joue un rôle critique", dit Dr Julian Knight, coauteur. "Si trop peu de vitamine est disponible, il est possible que le gène ne puisse pas fonctionner correctement". Ce gène agit sur le système immunitaire (rappelons que la SEP est une maladie auto-immune).
Cette étude suggère que de prendre des compléments de vitamine D durant la grossesse et durant les premières années pourrait réduire le risque de développer la SEP plus tard dans la vie", selon Dr Sreeram Ramagopalan qui a dirigé la recherche. (Il est difficile de combler les besoins en vitamine D par l'alimentation).
Psychomédia avec source:
Science Daily
Vitamin D is ray of sunshine for multiple sclerosis patients
Melanie Reid and Oliver Gillie
Times Online
Thu, 05 Feb 2009
Multiple sclerosis could be prevented through daily vitamin D supplements, scientists told The Times last night.
The first causal link has been established between the "sunshine vitamin" and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune disease could be eradicated.
George Ebers, Professor of Clinical Neurology at the University of Oxford, claimed that there was hard evidence directly relating both genes and the environment to the origins of MS.
His work suggests that vitamin D deficiency during pregnancy and childhood may increase the risk of a child developing the diease.
He has also established the possibility that genetic vulnerability to MS, apparently initiated by lack of vitamin D, may be passed through families.
These risks might plausibly be reduced by giving vitamin D supplements to pregnant woman and young children.
"I think it offers the potential for treatment which might prevent MS in the future," Professor Ebers said.
"Our research has married two key pieces of the puzzle. The interaction of vitamin D with the gene is very specific and it seems most unlikely to be a coincidence of any kind."
Warnings over sun exposure could now also be called into question - sunlight allows the body to produce the vitamin.
Professor Ebers said: "Serious questions now arise over the wisdom of current advice to limit sun exposure and avoid sunbathing. We also need to give better advice and help to the public on vitamin D supplements, particularly pregnant and nursing mothers."
The news has momentous implications for Scotland and other northern countries, where the incidence of multiple sclerosis is the highest in the world. It will give added urgency to recent moves by Scotland's Chief Medical Officer to consider recommending vitamin D supplements.
Deficiency in vitamin D, caused by lack of exposure to sunshine, has been increasingly linked to the cloudier climate in Scotland and other northern latitudes. The deficiency is twice as common among the Scots as it is amongst the English - and Orkney and Shetland have among the highest rates.
Studies have also shown that fewer people with MS are born in November and more in May, implicating a lack of sunshine during pregnancy.
The breakthrough comes after a groundswell of expert belief in the importance of vitamin D. Last November, at a conference organised by the Scottish Government, international experts urged vitamin D supplements for Scots to be tested "sooner rather than later" to find whether they could improve the nation's health.
Researchers for the World Health Organisation said there should be large, randomised trials as there was strong evidence that increased daily intake of vitamin D could significantly improve health.
The seminar followed evidence, revealed in The Times, that Scotland's poor health record has close links to vitamin D deficiency. Last September this newspaper reported evidence from scientists in Canada that children with early symptoms of multiple sclerosis have low levels of vitamin D.
Until now there has been no scientific proof of the links. However, Professor Ebers and his team have shown that vitamin D affects a particular genetic variant, identified as the one that increases the risk of developing MS threefold.
They suggest that a shortage of the vitamin alters this variant, thus preventing the immune system from functioning normally.
Professor Ebers said: "Whether it's at the core of MS is going to take some further work, but it does look like a reasonably good chance."
Last October Professor Ebers, in an article in The Times, backed the idea of distributing vitamin D supplements in Scotland to guard against conditions that may be linked to a deficiency, including MS.
"It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children," he wrote.
"Over a trial duration of 25 years, 5,000 cases of this disease might be otherwise prevented.
"The economic impact of each person with MS is at least an extra million pounds during a lifetime.
"Over 25 years £5 billion is at issue in this disease without factoring in the human cost, the increasing rate of MS or inflation. A large-scale programme providing vitamin D could provide scientific evidence."
Disease of the North: MS rates per 100,000 of the population
Canada 240
Scotland 150 - 200
Norway 110
England and Wales 90 - 110
Australia 78
Spain 59
Brazil 18
Sources: Atlas of Multiple Sclerosis
Times Online
Thu, 05 Feb 2009
Multiple sclerosis could be prevented through daily vitamin D supplements, scientists told The Times last night.
The first causal link has been established between the "sunshine vitamin" and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune disease could be eradicated.
George Ebers, Professor of Clinical Neurology at the University of Oxford, claimed that there was hard evidence directly relating both genes and the environment to the origins of MS.
His work suggests that vitamin D deficiency during pregnancy and childhood may increase the risk of a child developing the diease.
He has also established the possibility that genetic vulnerability to MS, apparently initiated by lack of vitamin D, may be passed through families.
These risks might plausibly be reduced by giving vitamin D supplements to pregnant woman and young children.
"I think it offers the potential for treatment which might prevent MS in the future," Professor Ebers said.
"Our research has married two key pieces of the puzzle. The interaction of vitamin D with the gene is very specific and it seems most unlikely to be a coincidence of any kind."
Warnings over sun exposure could now also be called into question - sunlight allows the body to produce the vitamin.
Professor Ebers said: "Serious questions now arise over the wisdom of current advice to limit sun exposure and avoid sunbathing. We also need to give better advice and help to the public on vitamin D supplements, particularly pregnant and nursing mothers."
The news has momentous implications for Scotland and other northern countries, where the incidence of multiple sclerosis is the highest in the world. It will give added urgency to recent moves by Scotland's Chief Medical Officer to consider recommending vitamin D supplements.
Deficiency in vitamin D, caused by lack of exposure to sunshine, has been increasingly linked to the cloudier climate in Scotland and other northern latitudes. The deficiency is twice as common among the Scots as it is amongst the English - and Orkney and Shetland have among the highest rates.
Studies have also shown that fewer people with MS are born in November and more in May, implicating a lack of sunshine during pregnancy.
The breakthrough comes after a groundswell of expert belief in the importance of vitamin D. Last November, at a conference organised by the Scottish Government, international experts urged vitamin D supplements for Scots to be tested "sooner rather than later" to find whether they could improve the nation's health.
Researchers for the World Health Organisation said there should be large, randomised trials as there was strong evidence that increased daily intake of vitamin D could significantly improve health.
The seminar followed evidence, revealed in The Times, that Scotland's poor health record has close links to vitamin D deficiency. Last September this newspaper reported evidence from scientists in Canada that children with early symptoms of multiple sclerosis have low levels of vitamin D.
Until now there has been no scientific proof of the links. However, Professor Ebers and his team have shown that vitamin D affects a particular genetic variant, identified as the one that increases the risk of developing MS threefold.
They suggest that a shortage of the vitamin alters this variant, thus preventing the immune system from functioning normally.
Professor Ebers said: "Whether it's at the core of MS is going to take some further work, but it does look like a reasonably good chance."
Last October Professor Ebers, in an article in The Times, backed the idea of distributing vitamin D supplements in Scotland to guard against conditions that may be linked to a deficiency, including MS.
"It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children," he wrote.
"Over a trial duration of 25 years, 5,000 cases of this disease might be otherwise prevented.
"The economic impact of each person with MS is at least an extra million pounds during a lifetime.
"Over 25 years £5 billion is at issue in this disease without factoring in the human cost, the increasing rate of MS or inflation. A large-scale programme providing vitamin D could provide scientific evidence."
Disease of the North: MS rates per 100,000 of the population
Canada 240
Scotland 150 - 200
Norway 110
England and Wales 90 - 110
Australia 78
Spain 59
Brazil 18
Sources: Atlas of Multiple Sclerosis
lundi 2 février 2009
Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study
The Lancet Neurology, Early Online Publication, 30 January 2009
Background
Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.
Methods
Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation.
Findings
Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8—11) and patients were discharged from hospital on mean day 11 (range day 8—13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24—48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0·0001), neurological rating scale score (p=0·0001), paced auditory serial addition test (p=0·014), 25-foot walk (p<0·0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0·0001).
Interpretation
Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.
Funding
Division of Immunotherapy, Northwestern University.
Background
Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.
Methods
Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 μg per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation.
Findings
Between January, 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8—11) and patients were discharged from hospital on mean day 11 (range day 8—13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24—48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0·0001), neurological rating scale score (p=0·0001), paced auditory serial addition test (p=0·014), 25-foot walk (p<0·0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0·0001).
Interpretation
Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.
Funding
Division of Immunotherapy, Northwestern University.
Cellules souches - Résultats encourageants contre la sclérose en plaque
Cécile Dumas
Sciences-et-Avenir.com
30/01/09
Un petit essai clinique, mené sur 21 personnes atteintes de sclérose en plaques, montre qu’une ‘auto-greffe’ de cellules souches issues de la moelle osseuse permet d'améliorer l’état des patients. Ces résultats encourageants devront être vérifiés sur une plus large cohorte et comparés à d’autres traitements pour être consolidés.
Environ 80.000 personnes en France souffrent de cette maladie dont les formes et l’évolution varient grandement d’un patient à l’autre. La sclérose en plaque est caractérisée par une destruction de la myéline, la couche protectrice qui entoure les fibres nerveuses et qui transporte l’influx nerveux. Troubles de la coordination, problèmes de vue, vertiges, problèmes moteurs sont quelques-uns des symptômes de la maladie.
Il s’agit d’une affection auto-immune, autrement dit d’une attaque du système immunitaire, via des lymphocytes devenus agressifs, qui s’en prennent à l’organisme lui-même (en l’occurrence à la myéline). C’est pourquoi des chercheurs essaient de ‘’reprogrammer’’ le système immunitaire en greffant des cellules souches hématopoïétiques, issues de la moelle osseuse, précurseurs des globules rouges et des globules blancs (dont font partie les lymphocytes).
L’équipe de Richard Burt, de Chicago (USA), a prélevé des cellules souches hématopoïétiques chez les patients. Ceux-ci ont ensuite subi un traitement destiné à détruire les lymphocytes qui attaquent leur myéline avant de recevoir une greffe autologue de cellules souches. Trois ans après, 17 patients sur 21 ont connu une amélioration de leur état (définie comme un point gagné sur l’échelle de Kurtzke utilisée pour décrire l’évolution de la maladie)*.
Ce n’est pas la première fois que cette technique est testée sur des personnes mais les précédents essais n’avaient pas obtenus de résultats concluants. La différence tient à l’âge des patients et au stade de la maladie : il s’agit de trentenaires dont la sclérose évolue par poussées, suivies de périodes de rémissions. C’est généralement la première phase de la maladie (dite forme rémittente), suivie d’une phase progressive où les symptômes semblent irréversibles.
* Travaux publiés en ligne (édition anticipée) par The Lancet Neurology (en mars dans la revue papier).
Sciences-et-Avenir.com
30/01/09
Un petit essai clinique, mené sur 21 personnes atteintes de sclérose en plaques, montre qu’une ‘auto-greffe’ de cellules souches issues de la moelle osseuse permet d'améliorer l’état des patients. Ces résultats encourageants devront être vérifiés sur une plus large cohorte et comparés à d’autres traitements pour être consolidés.
Environ 80.000 personnes en France souffrent de cette maladie dont les formes et l’évolution varient grandement d’un patient à l’autre. La sclérose en plaque est caractérisée par une destruction de la myéline, la couche protectrice qui entoure les fibres nerveuses et qui transporte l’influx nerveux. Troubles de la coordination, problèmes de vue, vertiges, problèmes moteurs sont quelques-uns des symptômes de la maladie.
Il s’agit d’une affection auto-immune, autrement dit d’une attaque du système immunitaire, via des lymphocytes devenus agressifs, qui s’en prennent à l’organisme lui-même (en l’occurrence à la myéline). C’est pourquoi des chercheurs essaient de ‘’reprogrammer’’ le système immunitaire en greffant des cellules souches hématopoïétiques, issues de la moelle osseuse, précurseurs des globules rouges et des globules blancs (dont font partie les lymphocytes).
L’équipe de Richard Burt, de Chicago (USA), a prélevé des cellules souches hématopoïétiques chez les patients. Ceux-ci ont ensuite subi un traitement destiné à détruire les lymphocytes qui attaquent leur myéline avant de recevoir une greffe autologue de cellules souches. Trois ans après, 17 patients sur 21 ont connu une amélioration de leur état (définie comme un point gagné sur l’échelle de Kurtzke utilisée pour décrire l’évolution de la maladie)*.
Ce n’est pas la première fois que cette technique est testée sur des personnes mais les précédents essais n’avaient pas obtenus de résultats concluants. La différence tient à l’âge des patients et au stade de la maladie : il s’agit de trentenaires dont la sclérose évolue par poussées, suivies de périodes de rémissions. C’est généralement la première phase de la maladie (dite forme rémittente), suivie d’une phase progressive où les symptômes semblent irréversibles.
* Travaux publiés en ligne (édition anticipée) par The Lancet Neurology (en mars dans la revue papier).
Turning down gene expression promotes nerve cell maintenance
February 2nd, 2009
Anyone with a sweet tooth knows that too much of a good thing can lead to negative consequences. The same can be said about the signals that help maintain nerve cells, as demonstrated in a new study of myelin, a protein key to efficient neuronal transmission.
Normal nerve cells have a myelin sheath, which, much like the insulation on a cable, allows for rapid and efficient signal conduction. However, in several diseases - the most well-known being multiple sclerosis - demyelination processes cause the breakdown of this "insulation", and lead to deficits in perception, movement, cognition, etc. Thus, in order to help patients of demyelinating disease, researchers are studying the pathways that control myelin formation and maintenance.
A new study by University of California scientists examines the role of a structural protein, called lamin, in maintaining myelin. They found that, while lamin is necessary in the initial stages of myelin formation, too much lamin promotes myelin breakdown. Further investigation led the researchers to the discovery of a signal that fine-tunes lamin expression. This signal, a microRNA called miR-23, can turn down lamin gene expression, and thereby prevent demyelination due to lamin overexpression.
This new work reported in Disease Models & Mechanisms (DMM), adds another piece to the puzzle that is understanding myelin formation and maintenance. Additionally, the identification of miR-23 as a myelin regulator introduces a new potential drug target in developing treatments for demyelinating illness.
The report was written Shu-Ting Lin and Ying-Hui Fu at the Department of Neurology, University of California San Francisco. The report is published in the March/April issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
Anyone with a sweet tooth knows that too much of a good thing can lead to negative consequences. The same can be said about the signals that help maintain nerve cells, as demonstrated in a new study of myelin, a protein key to efficient neuronal transmission.
Normal nerve cells have a myelin sheath, which, much like the insulation on a cable, allows for rapid and efficient signal conduction. However, in several diseases - the most well-known being multiple sclerosis - demyelination processes cause the breakdown of this "insulation", and lead to deficits in perception, movement, cognition, etc. Thus, in order to help patients of demyelinating disease, researchers are studying the pathways that control myelin formation and maintenance.
A new study by University of California scientists examines the role of a structural protein, called lamin, in maintaining myelin. They found that, while lamin is necessary in the initial stages of myelin formation, too much lamin promotes myelin breakdown. Further investigation led the researchers to the discovery of a signal that fine-tunes lamin expression. This signal, a microRNA called miR-23, can turn down lamin gene expression, and thereby prevent demyelination due to lamin overexpression.
This new work reported in Disease Models & Mechanisms (DMM), adds another piece to the puzzle that is understanding myelin formation and maintenance. Additionally, the identification of miR-23 as a myelin regulator introduces a new potential drug target in developing treatments for demyelinating illness.
The report was written Shu-Ting Lin and Ying-Hui Fu at the Department of Neurology, University of California San Francisco. The report is published in the March/April issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
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