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L'X fragile sera vaincu | Fragile X will be conquered

Archive for June, 2010

Pharma companies set their sights on autism

SFARI, Virginia Hugues

A decade of research on the biology of autism, combined with a steady rise in diagnoses, has finally piqued the pharmaceutical industry’s interest in developing drugs for the disorder.

In the past year, large pharmaceutical companies, small biotechs and academic groups have all jumped into the field, sponsoring clinical trials of both new and existing drugs. Preliminary data from one small clinical trial show positive results, and results from several others are expected this summer.

The autism community has long hoped for drugs that target the disorder’s hallmark social and communicative deficits. The only compounds approved by the U.S. Food and Drug Administration for autism — the antipsychotics risperidone and aripiprazole — alleviate secondary symptoms, such as irritability and aggression.

“For a while, we’ve been piggy-backing on drugs that have been indicated for other conditions, such as Alzheimer’s, because companies are not interested in developing a drug for a disorder that does not have a lot of market share,” says Antonio Hardan, associate professor of psychiatry and behavioral science at Stanford University.


Breaking the Steel Wall of Mental Retardation

TheWhip.net – By Cesar Chelala – NEW YORK
I remember my friend’s face when he told me that his daughter had been born with a severe mental disability.

“It was as if somebody had pointed a gun to my head,” he told me.

For as long as they have been known, mental disabilities have been the cause of profound unhappiness in parents of children born with them as well as in the children themselves.

But now there is hope.

An experimental drug made by Novartis, a Swiss pharmaceutical firm, has been shown to improve behaviors associated with mental retardation and autism in people affected with fragile X syndrome, the most common inherited cause of these mental disabilities. Although the results have been obtained in a small clinical trial involving only a few dozen patients, this finding offers the possibility that further advances could be obtained in the near future.


New kids on the block

By By Penni Crabtree, SPECIAL TO THE UNION-TRIBUNE | Sunday, June 20, 2010 at 12:01 a.m.

. . .


Founded: 2007

Employees: 4

Product: Potential treatments for mental impairment disorders such as Fragile X syndrome and autism

When Jay Lichter read in the July 2007 journal of the National Academy of Science about a Nobel laureate’s theory for reversing an inherited form of mental impairment, the local venture capitalist had an “aha moment.”

That aha resulted in Afraxis, a tiny San Diego biotech that is developing a drug for treating Fragile X syndrome, the most common inherited cause of mental retardation and the most common known cause of autism.

Nobel winner Susumu Tonegawa, a professor of neuroscience at MIT, first proposed the idea of developing drugs for the syndrome after his lab reversed symptoms of the disorder in mice.

Tonegawa found that by inhibiting an enzyme called PAK, the symptoms of Fragile X reversed dramatically, both at the cellular and behavioral levels.

Fragile X is caused by a mutation in a single gene, which causes defects in dendrites, the signaling arms of neurons. Dendrites communicate through bumps, called spines, which become too numerous and misshapen with the gene defect.

In the mice experiments, inhibiting PAK reduced the number of spines and caused them to take on more normal shapes.

Lichter, managing director at San Diego’s Avalon Ventures, contacted Tonegawa and put together a licensing deal that involved MIT and another firm that could screen potential drug compounds against the gene target.

Now Afraxis has an experimental drug that appears to have a “profound effect” in reversing the damage caused by Fragile X and schizophrenia — at least in mice, said Lichter.

And while it’s a long way from mice to men — the company hopes to begin testing the drug in humans in 2012 — the early-stage work shows tremendous potential, said Lichter, who also serves as CEO for Afraxis.

“It is the first treatment that has actually been shown to reverse the disease, not just treat symptoms,” Lichter said. “We’re talking about growing new connections in the brain in places known to control thinking and behavior — that’s the goal, and the promise, of this.”


The fragility of genetics

The Irish Times – Claire O’Connell

When her daughter was diagnosed with Fragile X, Maria Panza says the isolation she felt was terrifying

‘IT’S LIKE a bomb has been dropped on you.”

That’s how Maria Panza from Co Kildare felt when she found out that her daughter Alesia (then aged two) had Fragile X, a genetic condition associated with a spectrum of learning difficulties, anxiety in social situations and delays in speech and language development.

The rare, inherited condition centres on the FMR-1 gene on the X chromosome and the full syndrome crops up in an estimated one in 4,000 boys and one in 6,000 girls, according to Panza.

She adds that as many as one in 130 females and one in 775 males are carriers of an FMR-1 “pre-mutation” for Fragile X, which can be linked with early menopause and Parkinson’s-like tremors in adulthood.


New Autism Drug Research by Cellceutix on Compound KM-391 Results in Significant Behavioral Changes

BEVERLY, MA–Cellceutix Corporation (OTCBB: CTIX) announced today that a new animal study of its compound for autism spectrum disorder, KM-391, once again demonstrated a positive impact on several measures of behavior associated with autism. As announced last week, Cellceutix expedited the research through a collaborative effort with InterEd Faculty of Clinical Research (IFCR) in India and the prestigious Cochin University of Science & Technology (CUSAT).

In the study, test subjects previously injected with a compound to simulate autistic behaviors were injected with an oxytocin antagonist to intensify the symptoms. Test subjects were divided into four groups, oxytocin antagonist only, oxytocin antagonist plus KM-391 (10 mg/kg), placebo alone and placebo plus KM-391 (10 mg/kg). Measurements were taken of autism related behaviors including: repetitive behavior, self-induced injury, sensitivity to touch, positioning correction, group dynamics, and curiosity. The procedure was repeated with the same animals on days 5 and 10. When KM-391 was given along with the oxytocin antagonist, there was a significant reduction in all 6 autism-related behaviors within 1 to 2 hours.

“We are extremely excited about the results from this phase of testing as it coincides with the previous research,” said Dr. Krishna Menon, Chief Scientific Officer of Cellceutix. “Having been involved in the research and development of extremely successful compounds in the past, I am very encouraged by the research results that we are achieving with KM-391 and its development potential as a treatment for autism. In our testing, we have simulated specific characteristics of an autistic brain and behavioral symptoms that result from them. KM-391 has been shown to significantly improve both the physical conditions in the brain and behaviors resulting in our animal models. We now have a basis to expect to emerge as a pharma industry leader in autism.”


Sur le train des MGLUR5

Beaucoup d’articles en français sur les MGLUR5 aujourd’hui (!) un allié commun dans la quête de traitements pour  l’X Fragile et la maladie d’Alzheimer:


Alzheimer |La perte de la mémoire mieux comprise

Vers un traitement plus ciblé

Selon les auteurs, cet effet toxique peut être contrecarré par des antagonistes du récepteur mGluR5, qui seraient donc une meilleure cible pour le traitement de la maladie que les récepteurs spécifiques au glutamate actuellement ciblés.

Le détail de ces travaux réalisés par des chercheurs du Centre national de la Recherche scientifique de France et de l’Université Northwestern est publié dans la revue Neuron.



Version plus détaillée

Paris, 10 juin 2010

Alzheimer : des récepteurs au glutamate identifiés comme une cible thérapeutique potentielle

Antoine Triller, directeur de l’« Institut de Biologie de l’Ecole Normale Supérieure » (Inserm U1024, CNRS/ENS Paris), et son équipe, en collaboration avec des chercheurs de l’université Northwestern (Chicago), viennent de mettre au jour un nouveau mécanisme responsable des troubles de la mémoire dans la phase initiale de la maladie d’Alzheimer. Leurs travaux paraissent le 10 juin dans la revue Neuron.

La maladie d’Alzheimer à un stade précoce se distingue par des troubles particuliers de la mémoire. Il a été démontré que cette défaillance implique des dysfonctionnements et des détériorations des synapses (zones de contact entre les neurones) dus aux oligomères béta-amyloïdes solubles (Aβo). En se déposant sur la membrane des neurones, ces derniers s’accumulent et forment des plaques amyloïdes extracellulaires. Ces plaques altèrent alors de façon significative et très rapide la plasticité synaptique. Dans cette étude, Antoine Triller et son équipe ont étudié les mécanismes expliquant comment ces amas de protéines amyloïdes, qui se fixent spécifiquement aux synapses, perturbent leur fonction, leur morphologie et leur maintien au cours du temps.


Messi, le petit géant

Mike Zeisberger, Agence QMI  – 09/06/2010

Vers la fin de la saison 2008-2009, deux buts de Messi on permis aux visiteurs barcelonais de défaire le Real Madrid par la marque de 6-2, à leur domicile du stade Santiago Bernabéu. Ce fut la pire humiliation subie par le club madrilène depuis 1930. Après chacun de ses buts, Messi a soulevé son maillot devant les caméras et les spectateurs, de manière à laisser voir un t-shirt portant la mention «Syndrome du X fragile». Ce fut sa manière d’attirer l’attention sur le sort des enfants aux prises avec une déficience intellectuelle.


Doctors find way to reverse autism effects

Times of India ! :

Malathy Iyer, TNN, Jun 8, 2010, 04.29am IST

MUMBAI: New research by a team of Bangalore-based scientists has given hope to those with emotional problems caused by the inheritance of a fragile X chromosome. The researchers, for the first time in the world, mapped defective connections between nerve cells in the emotional hub of the brain of mice who had Fragile X Syndrome. The research has just been published in the online edition of the US-based Proceedings of the National Academy of Sciences.

In humans, while a fragile X chromosome may be passed from one generation to the next with no debilitating effects, the syndrome does affect one in 4,000 men and one in 6,000 women. Upto 20% of boys with autism have the condition due to Fragile X.


NCBS, NYU Neuroscientists Identify Synaptic Defect In Brain Area Involved In Fragile X Syndrome

Researchers at India’s National Centre for Biological Sciences (NCBS) and New York University’s Center for Neural Science have identified novel synaptic defects in an area of the brain that is involved in the debilitating emotional symptoms of Fragile X Syndrome (FXS). FXS is the leading known genetic cause of autism and mental retardation.

The study, which appears in the journal the Proceedings of the National Academy of Sciences, is also of potential therapeutic significance—it showed that a brief pharmacological treatment is capable of correcting some of these synaptic deficits in mice genetically engineered to model FXS.


Study offers hope for inherited mental retardation

Around 15% of autism cases arise out of FXS or some known genetic defect – Seema Singh

Bangalore: For long it’s been held that inherited mental impairment cannot be treated, and pervasive developmental disorders such as autism, which affects one in 200 to one in 500 children, have remained a mystery. In new research, scientists have shown a reversal in brain defects that are involved in Fragile X Syndrome (FXS), the leading genetic cause of autism and mental retardation, offering hope that an effective cure may not be too distant.


Recherche: Regard neuf sur les retards mentaux

Recherche: Regard neuf sur les retards mentaux, Elisabeth Gordon |
NEUROSCIENCES. Autisme, X fragile, Williams: une chercheuse de l’Université de Lausanne a scruté la matière grise de patients atteints de ces déficiences intellectuelles.
Quelques millimètres cubes de plus ou de moins de matière grise: cela suffit pour provoquer des retards mentaux. C’est ce qu’a constaté une chercheuse de l’Université de Lausanne (Unil), après avoir scruté le cerveau de patients à l’aide d’une technique perfectionnée d’imagerie cérébrale.

Cherine Fahim, du Laboratoire de recherche expérimentale sur le comportement de l’Unil, s’est intéressée à trois types de déficiences intellectuelles: l’autisme, le syndrome de l’X fragile et celui de Williams. Les deux premiers – dont il existe de multiples formes – ont un certain nombre de symptômes communs: les personnes affectées ont notamment des difficultés à établir des interactions sociales et à communiquer avec leur entourage. Dans le cas du syndrome de Williams, «c’est l’inverse», précise la spécialiste de neurosciences cliniques; les enfants concernés sont «hypersociaux et ont un langage bien développé».


Drugs ‘improve social skills of autism sufferers’

June 02 2010 By Jeremy Laurance, Health Editor

… Initial results from a small trial of a drug called arbaclofen, presented at the International Meeting for Autism Research in Philadelphia last week, suggest it may improve social skills in people with fragile X syndrome and autism, including communication and sociability, and reduce outbursts of irritability. Fragile X affects one in 3,000 people worldwide and is the most common genetic cause of autism, with a quarter of fragile X males affected.

Randall Carpenter of Seaside Therapeutics in Cambridge, Massachusetts, which is testing the drug, told New Scientist: “People may learn more, learn to speak better, learn social skills and to be more communicative.”


Drug could get into the autistic mind

Celeste Biever, New Scientist

CAN people with autism take a pill to improve their social skills? For the first time, drugs are being tested that could address the social difficulties associated with autism and other learning disorders by tackling some of the brain chemistry thought to underlie them.

The only drugs currently prescribed to people with autism seek to dampen aggression and anxiety. The new drugs, now in the very early stages of clinical testing, address some of the classic symptoms of autism.

“People may learn more, learn to speak better, learn social skills and to be more communicative,” says Randall Carpenter of Seaside Therapeutics in Cambridge, Massachusetts, which is testing one of the drugs.

Geraldine Dawson, chief science officer at the charity Autism Speaks and a psychiatrist at the University of North Carolina at Chapel Hill, is equally enthusiastic about the prospect of a new class of drugs. “For the first time we are seeing drugs that could tackle core autism symptoms,” she says.


Researchers identify biological roles for fragile X protein

SFARI, Virginia Hughes

FMRP, the protein missing in fragile X syndrome, is proving to be one of the brain’s best multitaskers: it’s needed for the birth of new neurons, to regulate protein translation, and for maintaining the structural integrity of spiny neuronal projections, according to several new studies.

Scientists have been trying to pinpoint the role of FMRP, or fragile X mental retardation protein, since they first linked it to fragile X syndrome 19 years ago1. The new work supports the prevailing model that FMRP helps the brain make proteins at the synapse, the junction between neurons, even when the genetic instructions for doing so are located far away, in the nucleus.

FMRP is an RNA-binding protein, and cell-culture experiments have found that its presence curbs the translation of RNA into protein2. Bolstering this observation, mice that lack FMRP have excessive amounts of protein in their synapses, the junctions between neurons. The mutant mice also have abnormally long and dense dendritic spines — neuronal projections that receive signals from other cells — suggesting that FMRP aids in synaptic pruning, a crucial part of learning.