07 décembre 2008

It's not what the papers say, it's what they don't

Ben Goldacre
The Guardian

Writing this column really scares me because I wonder whether everything else in the media is as shamelessly, venally, manipulatively, one-sidedly, selectively reported on as the things I know about. But this week the reality editing was truly without comparison.

On Tuesday the Telegraph, the Independent, the Mirror, the Express, the Mail, and the Metro all reported that a coroner was hearing the case of a toddler who died after receiving the MMR vaccine, which the parents blamed for their loss. Toddler 'died after MMR jab' (Metro), 'Healthy' baby died after MMR jab (Independent), you know the headlines by now.

On Thursday the coroner announced his verdict: the vaccine played no part in this child's death. So far, of the papers above, only the Telegraph has had the decency to cover the outcome. The Independent, the Mirror, the Express, the Mail, and the Metro have all decided that their readers are better off not knowing. Tick, tock.

Does it stop there? No. Amateur physicians have long enjoyed speculating that MMR and other vaccinations are somehow "harmful to the immune system" and responsible for the rise in conditions such as asthma and hay fever. Doubtless they must have been waiting some time for evidence to appear.

This month a significant paper was published by Hviid and Melbye in the December 1 issue of the American Journal of Epidemiology. They examined 871,234 children in a Danish birth cohort, comparing asthma in those who had MMR against those who didn't. MMR-vaccinated children were massively and significantly less often hospitalised with an asthma diagnosis, and used fewer courses of anti-asthma medication than unvaccinated children. This "protective" effect of the MMR vaccine was more pronounced for hospitalisations with severe asthma diagnoses.

Those results aren't just incompatible with an increased risk of asthma following MMR vaccination, they actually support the hypothesis that MMR vaccination is associated with a reduced risk of asthma in young children. Tick, tock.

And most astonishing of all is the tale of "the Uhlmann paper", or the "O'Leary paper". This came out in 2002 and claimed to have found evidence of vaccine measles virus in tissue samples from children with autism and bowel problems, to massive media acclaim.

As I've said previously, two similar papers, by Afzal et al and D'Souza et al, in 2006 found negative results on almost the same question, and were unanimously ignored by the media (even though D'Souza actively went out of his way to show how O'Leary et al got false positives).

Stephen Bustin is professor of molecular science at Barts and the London. He examined the O'Leary lab for the court case against MMR, as an expert witness for the drug company defendants. The case collapsed, and he was unable to discuss his findings. Then he was called to give evidence in the American "autism omnibus" case against the vaccine. The anti-vaccine movement did their best to prevent this. They knew what he had found: it appears to be incontrovertible evidence that the lab was detecting false positives.

Now Bustin has finally been able to write about what he found in O'Leary's lab. He published this month. Nobody who covered the original O'Leary paper has written about it. Not a soul will.

Measles cases are rising. Middle class parents are not to blame, even if they do lack rhetorical panache when you try to have a discussion with them about it.

They have been systematically and vigorously misled by the media, the people with access to all the information, who still choose, collectively, between themselves, so robustly that it might almost be a conspiracy, to give you only half the facts.

Today, I have merely given you some small part of the other half, and next week I will move on: but know that nobody else has.

01 décembre 2008

Brain's magnetic fields reveal language delays in autism

Psychology & Sociology

Faint magnetic signals from brain activity in children with autism show that those children process sound and language differently from non-autistic children. Identifying and classifying these brain response patterns may allow researchers to more accurately diagnose autism and possibly aid in developing more effective treatments for the developmental disorder. Timing appears to be crucial. "Children with autism respond a fraction of a second more slowly than healthy children to vowel sounds and tones," said study leader Timothy Roberts, Ph.D., vice chair of radiology research and holder of the Oberkircher Family Endowed Chair in Pediatric Radiology at The Children's Hospital of Philadelphia. Roberts used a technology called magnetoencephalography (MEG), which detects magnetic fields in the brain, just as electroencephalography (EEG) detects electrical fields.

Roberts presented his findings today at the annual meeting of the Radiological Society of North America in Chicago. "The brain's electrical signals generate tiny magnetic fields, which change with each sensation, and with communication among different locations in the brain," he added.

Roberts is working to develop "neural signatures" that can link recorded brain activity to particular behaviors in children with autistic spectrum disorders (ASDs), which are characterized by impaired development in communications and social functioning. "Our hypothesis is that speech and other sounds come in too fast for children with ASDs, and their difficulties in processing sound may impair their language and communication skills," said Roberts.

Physicians already use MEG to map the locations of abnormal brain activity in epilepsy, but the technology Roberts used is one of the few MEG machines available in a dedicated pediatric facility. In the current study, the researchers evaluated 64 children aged six to 15 at The Children's Hospital of Philadelphia. Thirty children had ASDs, the rest were age-matched, typically developing control subjects.

The MEG machine has a helmet that surrounds the child's head. The researchers presented a series of recorded beeps, vowels and sentences. As the child's brain responded to each sound, noninvasive magnetic detectors in the machine analyzed the brain's changing magnetic fields.

When sounds were presented, the MEG recorded a delay of 20 milliseconds (1/50 of a second) in the brain's response for children with ASDs, when compared with healthy control subjects. "This delay indicates that auditory processing is abnormal in children with autism, and may lead to a cascade of delay and overload in further processing of sound and speech," said Roberts. "Further research may shed light on how this delay in processing sounds may be related to interconnections among parts of the brain." Other testing, measuring a response to mismatched or changed sounds, found longer delays, up to 50 milliseconds (1/20 of a second).

Because autism disorders range across a spectrum of functional abilities, explained Roberts, neural signatures based on brain responses may allow clinicians to more accurately diagnose which subtype of ASD an individual patient has. Such diagnoses may be possible at an earlier age if future studies show that such signatures are detectable in infancy—at younger ages than in the children involved in the current study. "Earlier diagnosis of ASDs may allow clinicians to intervene earlier with possible treatments," said Roberts.

Furthermore, added Roberts, if a patient's neural signature overlaps with that found in another neurological condition, such as epilepsy or attention-deficit hyperactivity disorder, for which a treatment exists, that patient may benefit from such a treatment.

15 octobre 2008

Les Français ne sont pas assez vaccinés

Les Français ne sont pas assez vaccinés et on peut s'attendre à une recrudescence de maladies telles que la rougeole, la tuberculose, la coqueluche ou l'hépatite B, ont souligné mercredi des spécialistes lors d'une séance spéciale de l'Académie de Pharmacie.

Daniel Floret, président du comité technique des vaccinations, a noté que les Français étaient "les cancres de l'Europe" pour la vaccination contre l'hépatite B, avec un taux de couverture de 30%, suite aux polémiques sur le lien avec la sclérose en plaques.

"On attend une hausse de l'incidence de la maladie", a-t-il affirmé, de nombreuses personnes non vaccinées entrant dans la période la plus "à risque" (20-30 ans).

Pour la rougeole, le taux de couverture est un peu insuffisant et on assiste à "des flambées épidémiques". Pour le BCG, l'obligation vaccinale a été suspendue mais "il faut vacciner les enfants à risque", notamment ceux d'Ile-de-France ou issus de l'immigration.

Pour la coqueluche, les bébés pas encore vaccinés risquent d'être contaminés par des adultes qui ne sont plus immunisés. Il cite ainsi le cas de "17 nourrissons" atteints à Lyon au cours de la dernière année.

Le Pr Floret a évoqué aussi les risques de grippes nosocomiales, les infirmières étant "moins vaccinées" que l'ensemble de la population. Les soignants sont peu vaccinés aussi contre la coqueluche, la varicelle ou la rougeole.

Le Pr Jean-François Bach, secrétaire perpétuel de l'Académie des sciences, a admis qu'il y avait des risques vaccinaux mais "très rares" : "bécégite", une inflammation d'après BCG, paralysies du nerf facial après administration d'un vaccin nasal contre la grippe, réactions après vaccination contre la rougeole en Afrique...

En revanche les spécialistes se sont insurgés contre les effets secondaires "non prouvés" : autisme attribué au vaccin contre la coqueluche dans les années 80 en Grande-Bretagne, diabète attribué au BCG aux Etats-Unis, sclérose en plaques liée à la vaccination contre l'hépatite B en France.

Le Pr Bach a souligné "l'énorme erreur statistique" de l'équipe menée par le Pr Marc Tardieu, qui a vu récemment une "tendance significative" à la sclérose en plaques dans un sous-groupe d'enfants traités par le vaccin. "On ne peut pas analyser des sous-groupes commes des groupes entiers", a-t-il souligné. "Le dossier est vide".

Le Pr Marc Girard, de l'Académie de médecine, a évoqué les "vaccins du futur" pour lesquels la recherche pourrait aboutir dans 5 à 10 ans, concernant par exemple la bronchiolite de l'enfant ou le paludisme. Les chercheurs travaillent aussi sur un nouveau vaccin contre la tuberculose, le BCG n'étant pas efficace chez l'adulte.

Des vaccins non plus préventifs mais thérapeutiques (une fois la maladie déclarée) contre le sida ou l'hépatite C sont envisageables à plus long terme, de même que contre des maladies non infectieuses tels cancers, Alzheimer ou athérosclérose. Mais selon le Pr Girard c'est encore aujourd'hui "un peu théorique".

04 septembre 2008

Autisme: une étude confirme l'absence de lien avec le vaccin anti-rougeole

WASHINGTON (AFP) - Une étude conduite aux Etats-Unis confirme l'absence de lien entre l'autisme et le vaccin combiné contre la rougeole, la rubéole et les oreillons ce qui, espèrent ses auteurs, va permettre de revenir à un taux normal de vaccination pour combattre des poussées épidémiques de ces infections.
(Publicité)

Cette recherche publiée mercredi dans la version en ligne du journal Public Library of Science, a tenté de reproduire les résultats d'une étude de 1998 conduite par le Dr Andrew Wakefield du Royal Free Hospital en Grande Bretagne selon laquelle il existerait un lien entre l'autisme et ce vaccin.

Le Dr Wakefield, dont les travaux avaient alors paru dans la revue le Lancet, a depuis officiellement demandé leur rétractation.

Des chercheurs de l'Université Columbia à New York et des Centres fédéraux américains de contrôle et de prévention des maladies (CDC) ont ainsi tenté de trouver des signes de la présence de marqueurs génétiques du virus de la rougeole dans des échantillons de tissus intestinaux prélevés sur 25 enfants autistes et souffrant également de problèmes gastro-intestinaux.

Ils ont comparé ces échantillons avec ceux provenant de 13 enfants du même âge ayant aussi les mêmes troubles intestinaux mais qui ne sont pas autistes.

Les tissus ont été analysés par trois laboratoires qui ignoraient de quels enfants ils provenaient.

"Cette étude montre sans aucun doute l'absence d'un lien entre autisme et le vaccin", concluent ces auteurs.

Ils ont aussi collecté auprès des parents et des médecins traitants des données sur les antécédents médicaux de ces enfants pour déterminer si l'apparition de leur autisme ou de leurs troubles intestinaux précédaient leur vaccination.

"Nous n'avons trouvé aucun lien entre le moment de la vaccination et l'apparition de problèmes intestinaux ou d'autisme", a dit dans un communiqué le Dr Mady Horni de l'Université Columbia, l'un des co-auteurs de cette étude.

Les responsables de santé publique aux Etats-Unis insistent depuis ces dernières années sur l'absence de risque posé par ce vaccin combiné ou d'autres vaccins destinés aux enfants face à des groupes de parents affirmant que ces vaccinations pourraient être responsables de l'autisme.

Un cour fédérale américaine (U.S Court of Federal Claims), saisie par des parents, examine cette question depuis près d'un an.

L'Institut américain de médecine, qui fait autorité, a publié plusieurs rapports concluant avec certitude à l'absence de relation entre l'autisme et ces vaccins.

Le refus de nombreux parents de faire vacciner leurs enfants contre les infections infantiles a contribué au plus grand nombre de cas de rougeole aux Etats-Unis et dans certains pays européens observés depuis de nombreuses années, soulignent les CDC.

La rougeole tue environ 250.000 personnes annuellement dans le monde dont la plupart du temps des enfants dans les pays pauvres.

Selon les statistiques des CDC, un enfant sur 150 est atteint d'autisme ou du syndrome d'Asperger aux Etats-Unis.

08 août 2008

Rougeole : l'Europe voit rouge

Par Destination Santé

La rougeole envahit l'Europe. Après la Suisse et l'Autriche elle s'attaque à l'Italie et au Royaume-Uni. De l'autre côté de la Manche, 461 cas ont été enregistrés depuis le début de l'année. Les autorités italiennes ont quant à elles comptabilisé… 2 079 cas entre septembre 2007 et mai 2008 !

Une véritable flambée épidémique à laquelle jusqu'à présent, la France est épargnée. En Italie l'épidémie a débuté dans la région du Piémont, affectant essentiellement des adolescents non vaccinés. Mais 15 régions sur 21 sont désormais touchées. En cause comme toujours, une trop faible couverture vaccinale. Certes des progrès ont été réalisés mais « ils restent insuffisants » soulignent les rédacteurs d'Eurosurveillance. Selon le ministère de la Santé italien, elle était de 88% en 2006 contre 84% en 2003.

Les autorités sanitaires anglaises et galloises s'alarment pour leur part, du caractère endémique de la rougeole. A tel point qu'elles demandent à tous les services de santé de vacciner le maximum d'enfants. Une mission loin d'être évidente. Au Royaume-Uni en effet, une rumeur –démentie depuis - selon laquelle la vaccination ROR aurait été liée à l'apparition de cas d'autisme a effrayé la population en 1998. A cette date, 92% des petits Britanniques étaient immunisés. En 2003 ils n'étaient plus que 79%. Un taux de couverture qui depuis, peine à remonter.

Source : Eurosurveillance, volume 13, 3 juillet 2008 ; 17 juillet 2008


La bêtise et n'en finit pas de faire des petites victimes.

17 juin 2008

Hépatite B : la France toujours à la traîne

Par Destination Santé

Plus de 10 ans après « l'affaire » du vaccin anti-hépatite B et de son rôle supposé dans l'apparition de cas de sclérose en plaques (SEP), la France nage toujours dans ses contradictions. Onze études ont déjà écarté toute relation entre la SEP et ce vaccin… Et pourtant rien n'y fait : les Français et une partie des professionnels de santé le boudent toujours. Petit retour sur une épine dans le pied, dont un récent rapport de l'OMS ravive le piquant…
(Publicité)

« Dix ans après, la France a encore du mal à augmenter sa couverture vaccinale contre l'hépatite B » nous explique sur un ton très diplomatique (devoir de réserve oblige !) Eric Laurent. Au bureau régional de l'OMS pour l'Europe, il est « Conseiller adjoint en charge du programme des vaccinations ». Un conseiller donc, qui rappelle à l'envi que « le rôle de l'OMS n'est certainement pas de critiquer ses Etats-Membres ».

Critiquer, peut-être pas… Mais l'Organisation sait trouver son franc-parler quand il s'agit de mettre en garde contre les risques sanitaires liés à des choix politiques hasardeux ! En 1998, elle ne s'était pas privée de dire son désaccord avec la décision – prise par Bernard Kouchner – de suspendre la vaccination systématique des adolescents contre l'hépatite B. « Vous savez, nous sommes en contact régulier avec les autorités sanitaires françaises. Mais la situation est délicate, la vaccination contre l'hépatite B est un dossier sensible en France ». Sensible et surtout explosif : avec une couverture vaccinale qui oscille entre 33% et 42%, notre pays prend le risque sérieux de laisser « filer » les cirrhoses et les cancers primitifs du foie…

Pourquoi sommes-nous les seuls en Europe à nous défier de ce vaccin, le seul encore très récemment, à protéger d'un cancer ? Pour Eric Laurent, l'affaire est entendue : c'est la campagne de vaccination de masse lancée contre l'hépatite B en 1997 qui serait en cause. « C'est connu, les populations établissent très facilement un lien de cause à effet entre un vaccin et un effet secondaire. En revanche, défaire ce lien est une entreprise beaucoup plus longue et difficile. Il y a un grand travail d'information à fournir de la part des autorités ».

Aussi bien en direction du public, que des professionnels de santé ? « Oui, tout à fait, il est impératif d'avoir une position claire sur le sujet. La France devrait peut-être lancer une vaste campagne médiatique afin de rassurer une fois pour toute ses citoyens quant à l'innocuité du vaccin. A l'instar de celle qui a été menée en Grande-Bretagne il y a 4 ans. Elle avait alors permis de réconcilier les Anglais avec le vaccin ROR ».

Source : Bulletin de l'OMS, 6 juin 2008 ; interview d'Eric Laurent, Conseiller adjoint en charge du programme des vaccinations, OMS/Europe, 13 juin 2008


"Contre la stupidité, les dieux eux-mêmes luttent en vain" écrivait Schiller. Après "l'affaire" (inexistante) du ROR, "l'affaire" toujours aussi inexistante du vaccin de l'hépatite B n'en finit pas de faire des victimes... de la bêtise humaine.

06 mai 2008

Vaccin rougeole et autisme: aucune évidence scientifique

Genève, 2 mai - L'hypothèse d'un lien entre la vaccination rougeole et l'autisme a été lancée en 1998 par Wakefield. Des millions de dollars ont été investis pour étudier cette hypothèse effrayante. Le verdict est tombé en 2001: il n'y a aucune évidence scientifique soutenant cette hypothèse. Si la vaccination était une cause d'autisme, le nombre d'autistes augmenterait lorsque la vaccination est introduite dans un pays ou que la proportion d'enfants vaccinés augmente: ce n'est pas le cas, puisque l'autisme continue à augmenter même quand la vaccination rougeole diminue! Si la vaccination était une cause d'autisme, les enfants non vaccinés devraient avoir un risque d'autisme plus faible que les enfants vaccinés: ce n'est pas le cas, l'autisme touchant un enfant sur 100-150, vaccinés ou non.

Si la vaccination était un facteur déclenchant de l'autisme, les problèmes devraient apparaître plus souvent après qu'avant un vaccin: ce n'est pas le cas, puisque les troubles régressifs commencent après le vaccin chez 16% des enfants et avant le vaccin chez 18% d'entre eux. En 2004, une enquête a révélé que Wakefield avait été grassement payé par des avocats espérant intenter un procès aux producteurs. Même sa pseudo-démonstration de résidus de vaccin dans les intestins d'enfants autistes a été invalidée. En 2008, affirmer que ses travaux ont été vérifiés est un mensonge et accuser tous les autres chercheurs d'être manipulés par l'industrie est ridicule. En 2008, affirmer que la vaccination ROR provoque l'autisme c'est nier volontairement toutes les évidences. Répéter une croyance personnelle, même émotionnelle, ne suffit pas à la rendre juste et détourne l'attention des vrais défis. Les enfants autistes et leurs parents méritent plus de considération: ils ont le droit que les recherches s'orientent vers les causes réelles de leurs souffrances.

Professeur François Ansermet, médecin-chef du Service Psychiatrie de l'enfant et de l'adolescent HUG, et professeur Claire-Anne Siegrist, médecin adjoint et directrice du Centre de vaccinologue de la Faculté de médecine de Genève.

28 mars 2008

Doctor in MMR row defends stance at disciplinary hearing

Three deny serious professional misconduct
Clinical care of children main concern, GMC told

* Karen McVeigh
* The Guardian

The doctor who first sparked widespread safety fears over the MMR vaccine said yesterday that his paramount concern was "clinical care" for children who had developed autism after being vaccinated.

Giving evidence for the first time at a General Medical Council disciplinary hearing, where he is accused of serious professional misconduct, Dr Andrew Wakefield also denied he was motivated by an interest in litigation. He defended the way he carried out research which caused national controversy and a drop in vaccine rates.

Claims against Wakefield, 51, and two other doctors relate to investigations for their study on 12 children with bowel disorders carried out between 1996 and 1998. It is alleged Wakefield accepted £50,000 for research to support parents' attempts to fight for compensation.

Wakefield said: "In a research capacity, I was fascinated by the possibility that something could be done to help those children in their plight, but it was secondary to getting help for them. The reason those parents were contacting me was nothing to do with litigation."

Wakefield, a senior lecturer and academic who admitted at the hearing he had no knowledge of autism, nor any qualifications in paediatrics or pathology, also denied submitting young children to a series of painful tests in an attempt to stand up his hypothesis.

He said he had "no role whatsoever in determining clinically whether those tests should or shouldn't take place". He said all the tests were ordered by Professor John Walker-Smith, one of his co-accused. He referred to Walker-Smith as "one of the most eminent paediatric gastroenterologists in the world".

Earlier, Wakefield and his wife, Carmel, were cheered by about 60 supporters as they arrived at the hearing in central London.

Wakefield said he first published a paper on a possible link between the measles vaccine and inflammatory bowel problems such as Crohn's disease in 1995, after which he received calls from parents, beginning with the mother of "child two". He said she told him a "compelling story" - that she believed her child had developed autism after receiving the MMR vaccine.

Wakefield, who resigned from the Royal Free hospital in north London over the row, now works at the Thoughtful House Centre for Children in Austin, Texas.

Wakefield, Walker-Smith and the third defendant, Professor Simon Murch, all deny serious professional misconduct. The hearing continues.

17 mars 2008

Autismes et vaccin: le retour

(Agence Science-Presse)

On croyait la controverse sur l’autisme morte, eh bien la voilà qui resurgit par la façade politique.

Maintes fois avancé, le lien entre vaccination et autisme constitue un mythe. Toutes les hypothèses qui ont été proposées, comme la présence de mercure, se sont révélées, après examens, sans fondements.

Or, voilà que le gouvernement américain rallume le feu. Au début du mois, on apprenait que celui-ci allait compenser un couple de Georgie qui alléguait que l’autisme de sa fille, Hannah, aujourd’hui âgée de 9 ans, avait été causé par les vaccins qui lui ont été administrés en 2000.

La décision du gouvernement ne dit pas spécifiquement que ces vaccins ont causé l’autisme, mais que les vaccins auraient « aggravé » un trouble cellulaire déjà existant —un trouble au niveau des mitochondries. Les experts interrogés un peu partout se sont dit stupéfaits —et inquiets de l’impact que cela pourrait avoir sur les campagnes de vaccination, avec tous les risques que cela entraînerait pour la santé publique. Le ministère de la Santé a refusé de commenter, et les documents relatifs à la décision n’ont pas été rendu publics.

Quelque 5000 autres familles ont déposé des plaintes similaires. Le quotidien Atlanta Journal and Constitution parle de deux autres familles qui ont déposé des plaintes similaires à celle de la famille d’Hannah, pointant du doigt le thimérosal, un des composés du vaccin à base de mercure, comme étant la cause de l’autisme. Ces deux causes doivent arriver en cour en mai.

Or, la piste du thimérosal a bel et bien été fouillée ces dernières années. Au Danemark, le thimérosal avait été éliminé des vaccins infantiles dès 1992. Une étude menée dans ce pays au début des années 2000 a révélé qu’après 1992, le nombre de cas d’autisme a... continué de grimper. Cette année encore, trois études distinctes ont échoué à trouver un lien entre thimérosal et autisme. L’une d’elles, publiée en janvier dans les Archives of General Psychiatry, a révélé qu’après le retrait du thimérosal des vaccins administrés en Californie, le taux d’autisme n’a pas baissé... là aussi, il a continué d’augmenter!

L’augmentation pourrait être une affaire de diagnostic. Il y a longtemps qu'on ne parle plus d’un autisme, mais de plusieurs degrés d’autisme, et les diagnostics se sont considérablement raffinés depuis l'époque où ces enfants étaient confondus avec les déficients mentaux.

L’autisme est un problème neurologique dont on ignore la cause; elle pourrait être génétique. Les symptômes n’apparaissent pas clairement avant l’âge de 3 ans —soit quelques mois après la vaccination contre la rougeole et la rubéole. Plusieurs médecins croient que c’est la raison pour laquelle tant de parents font spontanément ce lien.

Leaky gut autism theory doubted

BBC News

Children with autism do not appear to leak damaging proteins from their intestines, a study into the so-called "leaky gut" theory has suggested.

It has been claimed autistic children cannot fully digest proteins found in many foods - and that the resulting peptides escape and affect the brain.

But UK researchers found children with autism did not have more peptides in their urine than a control group.

They have published their findings in the Archives of Diseases in Childhood.

The "leaky gut" theory is based in part on the idea that vaccines such as MMR - given to immunise against measles, mumps and rubella - damage the wall of the intestines.

This causes the digestive problems which lead to the production of peptides, the theory goes.

To try to counter the effects of this, some parents of autistic children then reduce the amount of proteins such as gluten - found in wheat, oats, rye and barley - and casein - found in dairy products, such as milk, cheese and yogurt - in their child's diet.

Looking for a cure

But a team from Great Ormond Street Hospital, Guy's and St Thomas' Hospital and the University of Edinburgh have found no evidence of a higher level of peptides in the urine of autistic children.

They looked at 65 boys with autism and 158 without.

"It is very distressing to have a diagnosis of autism, a lifelong condition. Many families are driven to try out interventions which currently have no scientific basis," said Dr Hilary Cass of Great Ormond Street.

"Advocates of the leaky gut theory offer children a casein and gluten-free diet which as yet lacks an evidence base. Our research throws serious scientific doubt on the putative scientific basis of that diet."

But Paul Whiteley of the Autism Research Unit at Sunderland University said while the study appeared to have ruled out one reason why a gluten and casein-free diet may work, that did not mean it was not effective for some sufferers.

"It is very good news that more research is being carried out in this area. But evidence suggest that the diet does have beneficial effects for a proportion of those with autism, many of whom do suffer from bowel problems," he said.

"We need further investigation to find out if there are other reasons why it may work."

Benet Middleton of the National Autistic Society said there was an "urgent need" for more research into the efficacy of special diets for thos with autism.

"We are aware of anecdotal support for some dietary interventions, particularly those involving the exclusion of wheat and dairy products," he said.

"There is limited evidence about whether or not these diets are effective and concerns have been raised about their unregulated use."

12 février 2008

Some cases of autism may be traced to the immune system of mothers during pregnancy

UC-Davis discovery could lead to prenatal identification and prevention

(SACRAMENTO, Calif.) – New research from the UC Davis M.I.N.D. Institute and Center for Children’s Environmental Health has found that antibodies in the blood of mothers of children with autism bind to fetal brain cells, potentially interrupting healthy brain development. The study authors also found that the reaction was most common in mothers of children with the regressive form of autism, which occurs when a period of typical development is followed by loss of social and/or language skills. The findings, to be published in the March 2008 issue of Neurotoxicology, raise the possibility that the transfer of maternal antibodies during pregnancy is a risk factor for autism and, at some point, that a prenatal test and treatment could prevent the disorder for some children.

“While a growing body of research is dedicated to finding distinctions in the immune systems of children with autism, this is one of the first studies to identify immunological factors in mothers that could be linked to autism in the very earliest stages of life,” said Judy Van de Water, senior author of the study and professor of rheumatology, allergy and clinical immunology. “Our results should lead to more research on the prenatal environment and the onset of autism. We are also optimistic that in the future a prenatal test and therapeutic intervention preventing IgG exposure during pregnancy could protect some children from ever getting autism.”

Van de Water and her team began their research with blood samples from 123 mothers – 61 whose children have autism and 62 whose children are typically developing. They isolated IgG antibodies from the samples then exposed the antibody to fetal brain tissue by western blot analysis, which detects antibody reactivity to proteins. The outcome revealed a highly specific reactivity pattern to two fetal brain proteins in seven of the 61 samples from the autism group, six of which were from mothers of children who had regressive autism. None of the IgG samples from mothers in the control group produced this same result.

“We’re not entirely sure why the IgG response against fetal brain proteins was so specific for later onset autism,” said Van de Water. “It’s possible that early exposure to maternal antibodies sets in motion a biological path to autism with the behavioral outcomes not apparent until much later. It’s also possible that an environmental exposure sometime after birth could be required to set this process in motion. We are hopeful that this study will help build our understanding of the foundations of the regressive form of the disorder.”

Characteristic features of autism – social deficits, language impairments and limited, repetitive behaviors – are often clear early in an affected child’s life. Other children seem to progress normally until 12-to-24 months of age, when developmental milestones disappear. These distinct pathways have led clinicians to identify autism as one of two types – early onset or regressive – potentially with distinct causes and disease processes.

IgG antibodies are responsible for long-term immune system responses to infection, but they can also contribute to autoimmune diseases such as arthritis, multiple sclerosis and lupus. IgG also crosses the placenta in order to provide key immune system protectants to a growing fetus and newborn child, which is a key reason why Van de Water decided to investigate the role of IgG as a potential factor in autism.

Van de Water next wants to know if IgG in women during the time of their pregnancies produces the same response to fetal brain proteins. Women in the current study were two-to-five years beyond childbirth. She will now conduct the same study with women who are pregnant and already have a child with autism, because such women are much more likely to have another child with the disorder.

“If women in this next phase of the study give birth to a child eventually diagnosed with autism, blood analyses from all stages of her pregnancy will give us a clear picture of the immune system factors that were in play during gestation and could have altered her child’s neurodevelopment,” Van de Water said.

Other key next steps are to identify the specific proteins targeted by autism-specific maternal antibodies and their role in neurodevelopment and to determine whether or not exposure to maternal IgG during pregnancy leads to behavioral or social distinctions in offspring. Animal model studies are now under way to help answer these questions.

“Our outcome leads autism science in many new and exciting directions,” said Daniel Braunschweig, pre-doctoral fellow of immunology in the Van de Water lab, lead author of the current study and recent recipient of an Autism Speaks mentor fellowship to further pursue this research. “We now know we should be looking for the clues to the onset and pathology of autism much earlier than was initially assumed. Future studies should consider the immune system interactions between mother and child as a focal point in creating greater understanding of, and eventually finding effective preventions for, this complex neurodevelopmental disorder.”

“This finding is important because it provides important clues about the potential maternal contributions to autism risk in a subset of children who may develop autism,” said Isaac Pessah, director of the UC Davis Center for Children’s Environmental Health and professor of molecular biosciences. “We’re determined to find out what causes autism. Studies conducted in the Van de Water lab are giving us valuable insights as to when and where in the developmental process we should be looking for those causes.”

“We’re very interested in understanding the underlying causes of autism,” said Cindy Lawler, scientific program director at the National Institute of Environmental Health Sciences. “This finding, in combination with other new research findings coming from NIH-funded studies, demonstrates the complexity of this disorder and underscores the importance of understanding how the mother’s immune system can influence early brain development.”

###

The study, “Maternally Derived Antibodies Specific for Fetal Brain Proteins,” was funded by the National Institutes of Environmental Health Sciences, the U.S. Environmental Protection Agency and the M.I.N.D. Institute. A copy can be requested from newsroom@elsevier.com or downloaded at www.sciencedirect.com.

The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center that brings together clinicians, scientists, parents and educators for research on causes, treatments, preventions and cures for autism, fragile X syndrome, Tourette’s syndrome, attention-deficit/hyperactivity disorder and other neurodevelopmental disorders. For more information, visit www.mindinstitute.org.

The UC Davis Center for Children’s Environmental Health and Disease Prevention is a multi-disciplinary research effort established to examine how toxic chemicals may influence the development of autism in children. Toward that goal, the center is conducting two large-scale research projects: the Childhood Autism Risks from Genetics and the Environment (CHARGE) study and Markers of Autism Risk in Babies—Learning Early Signs (MARBLES) study. For more information, visit www.vetmed.ucdavis.edu/cceh.

Editor’s note: B-roll of blood sample processing for immunological studies of autism in the Van de Water lab is available on request.

05 février 2008

MMR links to autism dismissed by huge study

Sarah Boseley, The Guardian

There is no evidence to link the MMR vaccination to autism in children, according to a substantial new study published today.

In the biggest review conducted to date, scientists from Guy's Hospital in London, Manchester University and the Health Protection Agency, analysed the blood from 250 children and concluded that the vaccine could not be responsible.

The study, which was funded by the Department of Health and is published in the journal Archives of Disease in Childhood, was initiated five years ago and comes a decade after a scare about the vaccination - which protects against mumps, measles and rubella - led to a big drop in the number of children given the jab.

The theory put forward by Dr Andrew Wakefield and colleagues was that the measles virus in the MMR caused bowel disorder and subsequently autism.

However, the blood samples taken from all the children in today's study did not support that analysis. The research specifically looked for traces of measles virus in the blood of 250 children who had been given the MMR vaccination, 98 of whom had an autistic spectrum disorder.

The scientists found no difference in levels of measles virus or antibodies between those who had been diagnosed with autism and those who had not.

The tests also showed no signs of bowel disorders developing either.

The children, aged about 10 years old, had been given the first MMR jab but not all had the booster. The researchers found that those with autism or learning difficulties tended not to have had the second jab, which they say is of concern.

Professor David Salisbury, director of immunisation at the Department of Health, said: "It's natural for parents to worry about the health and wellbeing of their children and I hope this study will reassure them that there is no evidence linking the MMR vaccine to autism."

Public health experts will be hoping this study can lay to rest the controversy.

The Department of Health stressed the quality of the study and in a statement said it had "linked very careful assessment and diagnosis of a child's condition, with expert analysis of blood samples".

27 janvier 2008

Dental Tooth Fillings Containing Mercury Don't Affect Children's Brain Development, Study Suggests

ScienceDaily (Jan. 27, 2008) — Dental amalgam tooth fillings do not adversely affect children's brain development and neurological status, researchers report in the February issue of The Journal of the American Dental Association.

The authors of the report—members of a joint team from the University of Lisbon, Portugal, and the University of Washington, Seattle—studied the possible neurological effects of dental amalgam tooth restorations. Dental amalgam contains elemental mercury combined with other metals such as silver, copper, tin and zinc to form a safe, stable alloy. Dental amalgam has been used for generations to fill decayed teeth that might otherwise have been lost.

Beginning in 1997 and continuing for seven years, the authors studied 507 Portuguese children aged 8 through 12 years who received either amalgam or resin-based composite fillings. They conducted routine clinical neurological examinations to assess two types of neurological signs: hard (indicating damage to specific neural structures) and soft (subtle signs of central nervous system dysfunction that likely point to immature sensory-motor skills rather than to any structural damage in the brain). The researchers also evaluated the children for presence of tremor.

After seven years, the two groups of children did not differ in terms of the presence or absence of hard signs or tremor. They also didn't differ in terms of the presence or absence or severity of soft signs at any point. Also, as expected in healthy children, the severity of any neurological soft signs diminished as the children aged.

"Even at the levels of amalgam exposure in this study (a mean of 7.7-10.7 amalgam surfaces per subject across the seven years of follow-up)," the authors write, "[we] conclude that exposure to mercury from dental amalgam does not adversely affect neurological status.

"These data indicate the absence of a generalized negative effect on children's nervous system functions stemming from the presence of dental amalgam," they continue, "and while we cannot rule out potential adverse reactions in individual children, we found no indications of any."

JADA, a monthly journal, is the ADA's flagship publication and the most widely read scientific journal in dentistry.

Adapted from materials provided by American Dental Association.

20 décembre 2007

Inherited Retardation And Autism Corrected In Mice

ScienceDaily — Researchers at MIT's Picower Institute for Learning and Memory have corrected key symptoms of mental retardation and autism in mice. They have significantly alleviated a wide range of abnormalities due to fragile X syndrome by altering only a single gene, countering the effects of the fragile X mutation.

The work also indicates that a certain class of drugs could have the same effect. These drugs are not yet approved by the FDA, but will soon be entering into human clinical trials. There is currently no treatment or therapy for fragile X syndrome, whose symptoms include mental retardation, epilepsy, and abnormal body growth.

Fragile X syndrome (FXS), affecting 100,000 Americans, is the most common inherited cause of mental retardation and autism. The MIT researchers corrected FXS in mice modeling the disease. "These findings have major therapeutic implications for fragile X syndrome and autism," said study lead author Mark F. Bear, director of the Picower Institute and Picower Professor of Neuroscience at MIT.

The findings support the theory that many of FXS's psychiatric and neurological symptoms-learning disabilities, autistic behavior, childhood epilepsy- stem from too much activation of one of the brain's chief network managers-the metabotropic glutamate receptor mGluR5.

"Fragile X is a disorder of excess-excess synaptic connectivity, protein synthesis, memory extinction, body growth, excitability-and remarkably, all these excesses can be reduced by reducing mGluR5," said Bear, a Howard Hughes Medical Institute investigator.

Individuals with FXS have mutations in the X chromosome's FMR1 gene, which encodes the fragile X mental retardation protein, FMRP. The MIT study found that FMRP and mGluR5 are at opposite ends of a kind of molecular seesaw. They keep each other in check, and without FMRP, mGluR5 signals run rampant.

Bear and colleagues study how genes and environment interact to refine connections in the brain. Synapses are the brain's connectors and their modifications are the basis for all learning and memory. There's a growing consensus among researchers that developmental brain disorders such as FXS, autism and schizophrenia should be considered "synapsopathies"- diseases of synaptic development and plasticity (the ability to change in response to experience).

Dendritic spines--little nubs on neurons' branchlike projections-receive many of the synaptic inputs from other neurons. Abnormal spines have long been associated with various forms of human mental retardation. In FXS, spines are more numerous, longer and more spindly than they should be. Thin spines tend to form weak connections.

The research team found that a 50 percent reduction in mGluR5 fixed multiple defects in the fragile X mice. In addition to correcting dendritic spines, reduced mGluR5 improved altered brain development and memory, restored normal body growth, and reduced seizures-many of the symptoms experienced by humans with FXS.

The researchers used genetic engineering to reduce mGluR5, but the same thing could be accomplished by a drug. Although not yet approved by the FDA, mGluR5 blockers are entering into human clinical trials. "Insights gained by this study suggest novel therapeutic approaches, not only for fragile X but also for autism and mental retardation of unknown origin," Bear said.

Earlier this year, MIT Picower Institute researcher Susumu Tonegawa and colleagues reported positive results using a different approach to reversing FXS symptoms. Tonegawa and colleagues identified a key enzyme called p21-activated kinase, or PAK, that affects the number, size and shape of connections between neurons.

This research is scheduled to be published in the Dec. 20 issue of Neuron. In addition to Bear, authors include Brown University graduate student Gul Dolen; Picower Institute postdoctoral fellow Emily Osterweil, B.S. Shankaranarayana Rao of the National Institute of Mental Health and Neuroscience in India; MIT graduate students Gordon B. Smith and Benjamin D. Auerbach; and Sumantra Chattarji of the National Center for Biological Sciences and Tata Institute of Fundamental Research in India.

This work is supported by the National Institute of Mental Health; the National Institute of Child Health and Human Development; the National Fragile X Foundation; FRAXA, a Fragile X research foundation; and the Simons Foundation.

Adapted from materials provided by Massachusetts Institute of Technology.

07 décembre 2007

Missing Protein May Be Key To Autism

ScienceDaily — A missing brain protein may be one of the culprits behind autism and other brain disorders, researchers at MIT's Picower Institute for Learning and Memory report in the Dec. 6 issue of Neuron.

The protein helps synapses develop. Synapses--through which neurons communicate with one other-underlie our ability to learn and remember. Now Li-Huei Tsai, Picower Professor of Neuroscience at MIT, has uncovered an enzyme that is key to that protein's activity.

Synapses are complex structures consisting of ion channels, receptors and intricate protein complexes that all work together to send and receive signals. Improperly formed synapses could lead to mental retardation, and mutations in genes encoding certain synaptic proteins are associated with autism.

Tsai studies a kinase (kinases are enzymes that change proteins) called Cdk5. While Cdk5's best-known role is to help new neurons form and migrate to their correct positions during brain development, "emerging evidence supports an important role for Cdk5 at the synapse," she said.

To gain a better understanding of how Cdk5 promotes synapse formation, Tsai's lab looked into how Cdk5 interacts with synapse-inducing proteins-in particular, a protein called CASK. CASK--a key scaffolding protein-is one of the first proteins on the scene of a developing synapse.

Scaffolding proteins such as CASK are like site managers, supporting protein-to-protein interactions to ensure that the resulting architecture is sound. Mutations in the genes responsible for Cdk5 and CASK have been found in mental retardation patients.

"We found that Cdk5 is critical for recruiting CASK to do its job for developing synapses," Tsai said. "Without Cdk5, CASK was not in the right place at the right time, and failed to interact with essential presynaptic components. This, in turn, led to problems with calcium influx." The flow of calcium in and out of neurons affects processes central to nervous system development and plasticity--its ability to change in response to experience.

Gene mutations and/or deletions in synaptic cell surface proteins and molecules called neurexins and neuroligins have been associated with autism. The problem with CASK recruitment investigated by the Tsai laboratory creates the same result as these genetic changes.

The Picower study also provides the first molecular explanation of how Cdk5, which also may go awry in neurodegenerative diseases such as Alzheimer's, promotes synapse development.

"There are still a lot of unknowns," said Tsai, who is also a Howard Hughes Medical Institute investigator. "Causes for psychiatric disorders are still very unclear, but accumulating evidence strongly suggests that alterations in the synaptogenesis program can lead to these serious diseases."

In addition to Tsai and Picower researcher Benjamin A. Samuels, co-authors are associated with Harvard Medical School; Johns Hopkins University School of Medicine; McLean Hospital in Belmont, Mass.; and Academia Sinica in Taiwan.

This work is supported by the National Institute of Neurological Disorders and Stroke (NINDS).

Adapted from materials provided by Massachusetts Institute of Technology.

30 novembre 2007

Autistic Children May Have Abnormal Functioning Of Mirror Neuron System

ScienceDaily (Nov. 29, 2007) — Using a novel imaging technique to study autistic children, researchers have found increased gray matter in the brain areas that govern social processing and learning by observation.

"Our findings suggest that the inability of autistic children to relate to people and life situations in an ordinary way may be the result of an abnormally functioning mirror neuron system," said lead author Manzar Ashtari, Ph.D., from the Children's Hospital of Philadelphia in Pennsylvania.

Mirror neurons are brain cells that are active both when an individual is performing an action and experiencing an emotion or sensation, and when that individual witnesses the same actions, emotions and sensations in others. First observed in the macaque monkey, researchers have found evidence of a similar system in humans that facilitates such functions as learning by seeing as well as doing, along with empathizing and understanding the intentions of others. Dr. Ashtari's study found the autistic children had increased gray matter in brain regions of the parietal lobes implicated in the mirror neuron system.

The study included 13 male patients diagnosed with high-functioning autism or Asperger syndrome and an IQ greater than 70 and 12 healthy control adolescents. Average age of the participants was about 11 years. Each of the patients underwent diffusion tensor imaging (DTI), a technique that tracks the movement of water molecules in the brain.

DTI is traditionally used to study the brain's white matter, as well as the brain fibers. However, Dr. Ashtari's team applied it to the assessment of gray matter by employing apparent diffusion coefficient based morphometry (ABM), a new method that highlights brain regions with potential gray matter volume changes. By adding ABM to DTI, the researchers can detect subtle regional or localized changes in the gray matter.

In addition to the gray matter abnormalities linked to the mirror neuron system, the results of this study revealed that the amount of gray matter in the left parietal area correlated with higher IQs in the control group, but not in the autistic children.

"In the normal brain, larger amounts of gray matter are associated with higher IQs," Dr. Ashtari said. "But in the autistic brain, increased gray matter does not correspond to IQ, because this gray matter is not functioning properly."

The autistic children also evidenced a significant decrease of gray matter in the right amygdala region that correlated with severity of social impairment. Children with lower gray matter volumes in this area of the brain had lower scores on reciprocity and social interaction measures.

"Impairments in these areas are the hallmark of autism spectrum disorders, and this finding may lead to greater understanding of the neurobiological underpinnings of the core features of autism," said study co-author Joel Bregman, M.D., medical director of the Fay J. Lindner Center for Autism.

Autism is the fastest growing developmental disability in the United States and typically appears during the first three years of life. Children with autism are hindered in the areas of social interaction and communication skills. According to the Centers for Disease Control and Prevention, as many as 1.5 million Americans have autism.

Results of the study conducted at the Fay J. Lindner Center for Autism, North Shore-Long Island Jewish Health System in Bethpage, N.Y., were presented November 28 at the annual meeting of the Radiological Society of North America.

Co-authors are S. Nichols, Ph.D., C. McIlree, M.S., L. Spritzer, B.S., A. Adesman, M.D., and B. Ardekani, Ph.D.

This study was supported by The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System and the National Center for Research Resources/National Institutes of Health.

Adapted from materials provided by Radiological Society of North America.

18 juillet 2007

The MMR story that wasn't

Whatever you think about Andrew Wakefield, the real villains of the MMR scandal are the media.

Ben Goldacre
Wednesday July 18, 2007
The Guardian

Whatever you think about Andrew Wakefield, the real villains of the MMR scandal are the media. Just one week before his GMC hearing, yet another factless "MMR causes autism" news story appeared: and even though it ran on the front page of our very own Observer, I am dismantling it on this page. We're all grown-ups around here.

The story made three key points: that new research has found an increase in the prevalence of autism to one in 58; that the lead academic on this study was so concerned he suggested raising the finding with public heath officials; and that two "leading researchers" on the team believe that the rise was due to MMR. Within a week the story had been recycled in several national newspapers, and the news pages of at least one academic journal.

But where did the facts come from? I contacted the Autism Research Centre in Cambridge: the study the Observer reported is not finished, and not published. The data has been collected, but it has not been analysed. Unpublished data is the antithesis of what science is about: transparency, where anyone can appraise the methods, and the results, and draw their own conclusions.

This study is the perfect example of why this is important: it was specifically designed to look at how different methods of assessing prevalence affected the final figure. So it is no surprise that one of the results from an early analysis is high, "one in 58", using techniques which deliberately cast the widest net. But even other figures in the initial analysis were less dramatic, and similar to current estimates, and the Observer admits it was aware of them. It seems it simply cherry picked the single most extreme number and made it a front page splash story.

The Observer is unrepentant: it says it has the "final report", from 2005. I can't get it to show it to me but the Cambridge team suspect the paper has seen the last of the quarterly progress reports to the funders. So how did the Observer manage to crowbar MMR into this story?

First, it claimed that the lead researcher, Professor Simon Baron Cohen, "was so concerned by the one in 58 figure that last year he proposed informing public health officials in the county." Prof Cohen is clear: this is inaccurate and scaremongering.

And the meat? The Observer claims that "two of the academics, leaders in their field, privately believe that the surprisingly high figure [one in 58] may be linked to the use of the controversial MMR vaccine." This point is repeatedly reiterated, with a couple of other scientists disagreeing to create that familiar, illusory equipoise of scientific opinion which has fuelled the MMR scare in the media for almost a decade now.

But in fact, the two "leading experts" who were concerned about MMR, the "experts", the "leaders in their field", were not professors, or fellows, or lecturers: they were research associates. I rang both, and both were very clear that they wouldn't describe themselves as "leading experts". One is Fiona Scott, a psychologist and very competent researcher at Cambridge. She said to me: "I absolutely do not think that the rise in autism is related to MMR." And: "My own daughter is getting vaccinated with the MMR jab on July 17."

She also said, astonishingly, that the Observer never even spoke to her. And in the Observer's "readers' editor" column one whole week later, where the Observer half heartedly addressed some of the criticisms of its piece, the Observer persisted in claiming she believes MMR causes autism: it believes it knows the opinions of this woman better than she knows her own mind. Despite her public protestations. The only voice that Dr Scott could find - bizarrely - was in the online comments underneath the readers' editor piece, where the Observer continued to call her an MMR "dissenter", and where she posted an impassioned and slightly desperate message, protesting her support of MMR, and threatening legal action.

That's one of the leading experts. The other is Carol Stott. She does believe that MMR causes autism (at last). However, she is no longer even a "research associate" at the Autism Research Centre.

Carol Stott works in Dr Andrew Wakefield's private autism clinic in America, which the Observer failed to mention, and she was also an adviser to the legal team which failed in seeking compensation for parents who believed that MMR caused their child's autism, which the Observer failed to mention. She was paid £100,000 of public money for her services. She says her objectivity was not affected by the sum, but even so this seems an astonishing pair of facts for the Observer to leave out.

And were Stott's views private, or secret, or new? Hardly. Stott is so committed to the cause against MMR that when the investigative journalist Brian Deer exposed the legal payouts in 2004, although she had no prior contact with him, she spontaneously fired off a long series of sweary emails titled "game on": "Try me, shit head ... Believe me, you will lose ... so go fuck yourself. Got it yet shit head. Try me ... Twathead ... waiting ... oh yes ... Stick that where it feels good. Shit head ... well, ur a bit slow on the uptake ... Give it time I s'pose. Twat." And so on.

On the phone I genuinely warmed to her, and she regrets that many people have fallen into entrenched positions on MMR on both sides. But she's not a leading expert (as she herself agrees); she's not a sombre Cambridge academic suddenly expressing a fresh concern (her views are very public); and in any case, even she is very clear that this new research reported in the Observer would tell us nothing whatsoever about MMR causing autism.

Nothing has changed, and this scare will never be allowed to die. If we had the right regulatory structures, almost every section of the media would be in the dock, alongside Wakefield.

26 juin 2007

Researchers Reverse Symptoms In Mice Of Leading Inherited Cause Of Mental Retardation

Science Daily — Researchers at the Picower Institute for Learning and Memory at MIT have, for the first time, reversed symptoms of mental retardation and autism in mice.

In Fragile X, there is a mutation in a gene called FMR1 on the X chromosome. (Credit: Image courtesy of NIH/National Human Genome Research Institute)

The work will be reported in the online early edition of the Proceedings of the National Academy of Sciences the week of June 25-29.

The mice were genetically manipulated to model Fragile X Syndrome (FXS), the leading inherited cause of mental retardation and the most common genetic cause of autism. The condition, tied to a mutated X chromosome gene called fragile X mental retardation 1 (FMR1) gene, causes mild learning disabilities to severe autism.

According to the Centers for Disease Control, FXS affects one in 4,000 males and one in 6,000 females of all races and ethnic groups. The prevalence of autism ranges from one in 500 to one in 166 children. There is no effective treatment for FXS and other types of autism.

"Our study suggests that inhibiting a certain enzyme in the brain could be an effective therapy for countering the debilitating symptoms of FXS in children, and possibly in autistic kids as well," said co-author Mansuo L. Hayashi, a former Picower Institute postdoctoral fellow currently at Merck Research Laboratories in Boston.

The study identifies a key enzyme-a chemical reaction-inducing protein-as a possible target for an FXS drug. The enzyme, called p21-activated kinase, or PAK, affects the number, size and shape of connections between neurons in the brain.

Halting PAK's enzymatic activity reversed the structural abnormality of neuronal connections found in the FXS mice, said co-author Susumu Tonegawa, 1987 Nobel laureate and Picower Professor of Biology and Neuroscience. "Strikingly, PAK inhibition also restored electrical communication between neurons in the brains of the FXS mice, correcting their behavioral abnormalities in the process," he said.

There are known chemical compounds that inhibit the enzymatic activity of PAK. These compounds or versions of them may be useful in the future development of drugs for treating FXS, he said.

"These are intriguing findings because the expression of the gene that inhibits PAK occurs in the third week after birth, which means that the neuronal abnormalities in the fragile X mouse are reversed after they appear," said Eric Klann, a professor at New York University's Center for Neural Science. "This is very exciting because it suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children."

Restoring neuronal connections

Tonegawa, Hayashi, MIT graduate student Bridget M. Dolan of the Department of Biology and colleagues study the molecules that govern the formation of neuronal connections in the brain. They explore how abnormalities in these molecules could interfere with an animal's behavior.

In the brain, small protrusions called dendritic spines on the branch-like dendrites of one neuron receive chemical signals from other neurons and communicate them to the main cell body. The numbers and shapes of dendritic spines are key to normal brain function.

FXS patients have higher numbers of dendritic spines in their brains, but each spine is longer and thinner, and transmits weaker electric signals, than those in non-affected individuals. When the enzymatic activity of PAK was inhibited in the FXS mice, abnormalities in their spine number and structure-as well as the weaker electrical communication between their neurons-were reversed.

Reversing behavioral symptoms

The FXS mice exhibited symptoms similar to those in FXS patients. These included hyperactivity; purposeless, repetitive movements reminiscent of autistic people; attention deficits and difficulty with learning and memory tasks.

"These behavioral abnormalities are ameliorated, partially or fully, by inhibiting the enzymatic activity of PAK," Tonegawa said. "Notably, due to an elegant genetic manipulation method employed by the Picower Institute researchers, PAK inhibition in the FXS mice did not take place until a few weeks after appearance of disease symptoms. This implies that future treatment may still be effective even after symptoms are already pronounced."

"While future studies will be necessary to further characterize the precise molecular nature of the interaction between PAK and FMR1, our findings clearly demonstrate that PAK inhibition can counteract several key cellular and behavioral symptoms of FXS," the authors noted.

In addition to Tonegawa, a Howard Hughes Medical Institute investigator, Hayashi and Dolan, authors include colleagues at the National Institute of Mental Health and Neurosciences; the Tata Institute of Fundamental Research in India; and Seoul National University in Korea.

This work was supported by the FRAXA Foundation, the Simons Foundation, the Wellcome Trust and the National Institutes of Health.

Note: This story has been adapted from a news release issued by Massachusetts Institute of Technology.

21 juin 2007

Protein mutations link to autism

Scientists have discovered how mutations in two key proteins may lead to autism.

They have shown one protein increases the excitability of nerve cells, while the other inhibits cell activity.

The University of Texas team found that in normal circumstances the proteins balance each other out.

But the study, published in Neuron, suggests that in people with autism the balance between the proteins is knocked out of kilter.

The findings back the theory that autism involves an imbalance between excitatory and inhibitory connections between nerve cells.

The proteins, which serve to physically link nerve cells together, were discovered by the team at the university's Southwestern Medical Center more than a decade ago.

However, until the latest study their exact function had been unclear.

Lead researcher Dr Ege Kavalali said: "Mutations in these proteins have recently been linked to certain varieties of autism.

"This work provides clear insight into how the proteins function. We can never design a therapeutic strategy without knowing what these mutations do."

Bridge between cells

The proteins - neuroligin-1 and neuroligin-2 - create a physical bridge at the junction - or synapse - of nerve cells, enabling them to make connections with others.

In studies on rats the researchers showed that raising levels of both proteins in nerve cells led to the creation of extra synapses.

Neuroligin-1 was associated with excitatory connections and neuroligin-2 with inhibitory connections.

When they introduced a mutant form of neuroligin-1 thought to be carried by some people with autism the number of synapses fell dramatically - and the cells became significantly less excitable.

Infants are born with far more synapses than survive to adulthood. Active synapses proliferate during development, but inactive synapses are culled.

The latest research suggests that carrying a mutant form of neuroligin-1 may depress the number of synapses that make it into adulthood.

This could hamper the ability of nerve cells to make the usual connections, and lead to the deficits seen in people with autism.

It affects the way a person communicates and interacts with other people.

Communication problems

People with autism cannot relate to others in a meaningful way. They also have trouble making sense of the world at large.

As a result, their ability to develop friendships is impaired. They also have a limited capacity to understand other people's feelings.

Autism is often also associated with learning disabilities.

Professor Simon Baron-Cohen, director of the Autism Research Centre at the University of Cambridge, said research into the role of neuroligins in autism was important.

He said: "We need to know more about both the genes that code for neuroligins, and the neuroligins themselves, to establish if they play a specific role in the cause of autism spectrum conditions and in which subgroup.

"Understanding how the autistic brain is different to the neurotypical brain will have significant implications for education and intervention."

06 juin 2007

Dan Olmsted, la propagation de rumeurs et la science

EDITORIAL

Dan Olmsted ferait mieux de s'occuper ne pas s'occuper de sujets qui le dépassent. Journaliste d'une série d'articles qui ne font que marteler les mêmes erreurs, dans l'espoir sans doute de les rendre plus crédibles, il finit surtout par lasser même les parents les plus crédules.

Dans le dernier opus, il nous parle des coïncidences et arrive à s'étonner lui-même. Ainsi, il affirme:
The autism rate rises in tandem with increasing numbers of vaccines that contain a known neurotoxin, ethyl mercury.

Public health authorities say that's coincidence.
Effectivement, les autorités médicales ont raison. Ce sont des coïncidences. Pour le prouver, il suffit d'en trouver d'autres. Le taux d'autisme augmente aussi avec l'utilisation des téléphones portables, des ordinateurs, de la crème solaire, des congés payés, de l'élargissement de la définition de l'autisme, etc. Bref, de tout ce qui augmente en fonction du temps. En statistiques, on appelle ça une corrélation temporelle. Dans le langage courant: une coïncidence.
Dan Olmsted oublie tout simplement de dire que la fameuse 'neurotoxine', le thimerosal, en fait un adjuvant permettant d'activer les défenses immunitaires et donc de limiter les doses et le nombre de piqures, a été retiré des vaccins infantiles depuis plus de dix ans et que le taux d'autisme n'a pas décru pour autant. Et ça, Mr Olmsted, ce n'est plus une coïncidence, c'est une démonstration de la fausseté flagrante de cette théorie.

Mr Olmsted continue dans son obsession:
Parents say their children became autistic after receiving mercury-containing vaccinations, sometimes several shots in one day.

Pediatricians call that coincidence, too.
Incroyable, l'autisme arrive dans une période de vaccin ! A-t-il eu des enfants ? Il suffit de calculer le nombres de vaccins que le nouveau-né reçoit dans les trois premières années de sa vie et de diviser par 36 pour savoir qu'il n'y a pas beaucoup de mois sans piqure. Quel est le risque qu'un autisme, qui se manifestera pendant ces trois premières années, soit remarqué à 15 jours maximum d'une piqure ? A peu près une chance sur une. Plus qu'il n'en faut pour que certains parents en quête de sens opèrent une corrélation douteuse.
Si l'autisme se déclenche aussi à chaque fois à moins de trois jours du dernier repas de votre bambin, faut-il aussi le priver de nourriture ? Ca aussi, c'est un événement qui a une chance sur un de se produire.
Rappelons encore que les vaccins, contrairement aux affirmations mensongères de Mr Olmsted ne comportent plus de thimerosal depuis plus de dix ans. Ou en est la fantastique décrue de l'autisme qu'on peut donc légitimement attendre depuis sept ans ?

Olmsted continue ses divagations:
Another remarkable fact that caught my attention: Autism was first identified in both the United States and Europe at almost exactly the same time. Child psychiatrist Leo Kanner published his landmark paper at Johns Hopkins University in Baltimore in 1943; pediatrician Hans Asperger published his -- about a slightly less severely affected group of children -- in Vienna in 1944. Cut off by a world war, neither knew of the other's work.

Coincidence, say the experts, who attribute the timing to improving diagnostic techniques in both countries.
Mr Olsmted devrait relire l'histoire des sciences. Il trouverait de nombreux exemples de ce genre de 'coïncidences'. Mais ce domaine n'est pas non plus son fort.

Et ici, il commence à affirmer sans la moindre preuve, sur la base de coïncidences avec des vaccins qui ne contiennent rien de ce qu'il prétend:
If it's not a coincidence that autism arose simultaneously on separate continents, that suggests something happened in two places at once to trigger the disorder.
Là, il affirme que l'autisme n'existait pas avant les vaccins et que ces troubles sont apparus juste à ce moment. Or l'autisme ne pouvait pas être diagnostiqué avant qu'on ait défini ce qu'on entend par là. Les cas d'autisme d'avant cette définition étaient classifiés parmi les "folies", "retard mentaux", etc. Normal qu'on ne trouve aucun cas d'autisme au moyen âge, le mot n'avait même pas été inventé. Ce qui ne veut pas dire que la chose que ce mot recouvre aujourd'hui n'existait pas. Mr Olmsted prétendrait certainement que l'ADN n'existait pas avant qu'on le découvre ! C'est la génération spontanée version XXIème siècle.

Et Mr Olmsted saute immédiatement sur une conclusion, assez bête puisque les cas génétiques ont été montrés par plusieurs études sérieuses (ce blog leur est dédié):
And that would suggest genes are not the fundamental factor, though they certainly could be implicated in making some children susceptible to whatever the new exposure was.
Récapitulons: le thimerosal aurait déclenché une épidémie d'autisme qui continuerait d'augmenter depuis dix ans malgré son retrait des vaccins. Les gènes ne seraient pas un facteur fondamental mais l'épidémie touche quatre fois plus de garçons que de filles, signe impliquant généralement une sensibilité génétique sur le chromosome X ou Y.

Et Olsmted rabâche le même mensonge ad libitum:
Remember, this type of mercury didn't exist in nature; it's man-made, and Kharasch is the man who made it marketable.
Il oublie une fois de plus que ce dont il parle n'existe plus. Il continue, de façon assez ridicule, en prévenant maintenant qu'il fait des hypothèses:
So what might have happened -- warning, hypothesis ahead -- is that some early exposures to ethyl mercury came from inhaling or otherwise coming into contact with it via that agricultural route. And some of the children exposed to this novel and neurotoxic form of mercury developed a novel neurological disorder called autism.
Là, Olmsted se rend compte qu'il fait des hypothèses ! Parce que jusqu'à présent, il croyait exposer des faits ! Et il dérape: maintenant il n'accuse plus les vaccins mais s'apprête à accuser les pesticides. Alors bien sûr, personne ne prétendrait qu'il est bon pour la santé de respirer des pesticides à hautes doses toute la journée. Il y a même des règlements de plus en plus sévères contre ça.
Olmsted change de produit, et passe du thimerosal aux pesticides. Quelle rigueur dans la pensée ! Donc les autismes se trouveraient principalement chez les agriculteurs, si nous comprenons bien le cheminement tortueux de cette personne. Très bien !

Olmsted continue ses imprécations:
Now check this out: Among the earliest cases seen in Europe were 10 identified by a Dutch researcher named D. Arn Van Krevelen. One of the 10 fathers was a horticulturalist; another was a florist's salesman.
Alors les agriculteurs qui vaporisent les pesticides à haute dose n'ont rien mais un pauvre fleuriste s'en prend plein la figure ! Là, Olmsted prend carrément les parents d'enfants autistes pour des imbéciles.

Je laisse la conclusion à Olmsted:
Maybe that's no coincidence.
En effet, il n'y en a pas: Olsmted est fait pour l'astrologie, les tarots et la lecture des lignes de la main. Vu son peu d'attachement aux faits réels, il devrait éviter la science et même le journalisme.