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

Archive for March, 2011

Asuragen Launches CE Marked IVD AmplideX™ Fragile X Test in Europe

Genengnews.com |

Asuragen, Inc. announced that they have achieved CE-marking and commercial launch in Europe of the AmplideX™ FMR1 PCR Kit for the detection of CGG repeats in the fragile X mental retardation (FMR1) gene. The AmplideX FMR1 PCR Kit is widely available through Asuragen’s recently established network of distributors in Europe. The AmplideX™ FMR1 PCR Kit is used as an aid in the diagnosis of fragile X syndrome and associated disorders, such as fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). The Kit provides a high throughput PCR and CE analysis workflow that can accurately resolve sample zygosity and reproducibly detect the full range of full mutation alleles in a single reaction. These assay capabilities reduce the need for Southern blot testing to 2% or less of all samples.

According to Dr. Sara Seneca from the University of Brussels, Belgium, “This new technology has distinct advantages over existing methodologies and was easy to adopt for routine use in our clinical lab.” Dr. David Barton from the National Centre for Medical Genetics in Dublin, Ireland, also commented that “We have gained substantial efficiencies since adopting the AmplideX Kit for our Fragile X testing.”

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Fragile X Researcher Honored by March of Dimes

cnbc.com |

Stephen T. Warren Receives 2011 Lifetime Achievement Award in Genetics A world-renowned fragile X syndrome researcher, who was the first to identify the long-sought genetic abnormality responsible for this disorder, will be honored by the March of Dimes.

Stephen T. Warren, PhD, the William Patterson Timmie Professor of Human Genetics and Charles Howard Candler chair of the Department of Human Genetics, as well as professor of biochemistry and pediatrics at Emory University School of Medicine, will receive the March of Dimes/Colonel Harland Sanders Award for Lifetime Achievement in the field of genetic sciences. Dr. Michael Katz, senior vice president for Research and Global Programs of the March of Dimes, will present the award to Dr. Warren today during the annual Clinical Genetics Meeting of the American College of Medical Genetics at Vancouver Convention Centre.

Fragile X syndrome is an inherited genetic condition that involves changes in the X chromosome and specifically the FMR1 gene. It is the leading cause of inherited intellectual disability. Fragile X can be passed on in a family by individuals who have no signs of this genetic condition. In 1991, Dr. Warren — initially funded by a March of Dimes Basil O’Connor Starter Scholar Award — and colleagues published their work on the genetic abnormality responsible for fragile X syndrome, as well as the affected protein. Dr. Warren has successfully applied his research findings to clinical settings.

Dr. Warren received his doctorate in human genetics in 1981 from Michigan State University and in 1985 joined the faculty of Emory University School of Medicine. Dr. Warren was elected to the Board of Directors of the American Society of Human Genetics in 1997 and elected its president in 2006. He was also editor-in-chief of The American Journal of Human Genetics from 1999 until 2005.

Dr. Warren has received many honors for his fragile X syndrome research, including the Albert E. Levy Faculty Award from Emory University, a MERIT award from the National Institutes of Health, the William Allan Award from the American Society of Human Genetics, and was elected to the Institute of Medicine of the National Academy of Science. He was also awarded the inaugural William Rosen Research Award from the National Fragile X Foundation.

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Fragile X Premutation Disorders – Expanding the Psychiatric Perspective

PubMed Central | ncbi.nlm.nih.gov |

Objective:

Fragile X premutation conditions are associated with a significant degree of psychopathology and thus are of interest to the psychiatrist. Remarkable advances at the molecular level have enhanced our understanding of fragile X premutation disorders.

Methods:

The authors review the genetic, molecular, neuroimaging, and clinical (systemic, neurologic, and psychiatric) manifestations of the premutation carrier state (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene.

Results:

Clinical manifestations of psychiatric illness in premutation carriers include cognitive, mood, anxiety, and other psychiatric disorders. Fragile X premutation-associated conditions are part of the clinical differential diagnosis of several psychiatric syndromes, particularly in pedigrees with known fragile X syndrome (FXS) cases.

Conclusions:

Fragile X-associated psychiatric manifestations serve as a useful model for a molecular genesis of neuropsychiatric illness. Because of the multigenerational expression of fragile X-associated neuropsychiatric illness, there is a prominent role for genetic testing and genetic counseling of patients and their relatives. Genetic testing is confirmatory of the FMR1 premutation and is an essential component of the clinical evaluation. Psychopharmacological and psychotherapeutic treatment of fragile X-associated psychiatric illnesses may improve patient function and assist in adaptation to the burden of a genetic neuropsychiatric illness.

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FMRP function throughout life leading to targeted treatments for FXS

PubMed Central / ncbi.nlm.nih.gov |

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FMRP is an mRNA-binding protein that is important for mRNA transport, mRNA stabilization and translation of mRNA into protein at the synapse [129-131]. FMRP is also a factor in the regulation of adult neurogenesis, so in the absence of FMRP there is dysregulation of glycogen synthase kinase (GSK)3β, reduced β-catenin and defective Wnt signaling. These alterations lead to downregulation of neurogenin 1, which is an early initiator of neuronal differentiation and an inhibitor of astrocyte differentiation [132]. Therefore, FMRP is important throughout life and there is a high incidence of motor problems, including Parkinson disease (PD), with aging in those with FXS [133]. In addition, in neuropathologic studies, there is evidence of migration problems in the hippocampus and in the cerebellum in those with FXS (Greco et al,. unpublished data), which are similar to those reported in individuals with autism [134]. These problems may be related to dysregulation of Wnt signaling in both FXS and autism.

Perhaps the most important change in protein expression in the absence of FMRP is the excess basal translation of proteins involved in the metabotropic glutamate receptor (mGluR) 5 receptor pathway [135]. Bear and colleagues have proposed the mGluR theory of FX, suggesting that the deficits associated with FXS are related to upregulation of the downstream effectors of the mGluR5 pathway, leading to enhanced long-term depression (LTD), and that treatment with an mGluR5 antagonist could be a targeted treatment for FXS [135,136]. Both FMRP and mGluRs play important roles in synaptogenesis and synaptic plasticity, and in the absence of FMRP there are long, thin and immature dendritic spines in both human and animal models of FXS [137-142]. There are also enhanced, abnormal epileptiform discharges consistent with an enhanced rate of clinical seizures in FXS [143,144].

Support for the ‘mGluR theory’ has been shown by generating FMR1 mutant mice with a 50% reduction in mGluR5 expression [145]. The mGluR5 deficiency rescued most of the KO mouse abnormalities including altered ocular dominance plasticity, increased density of dendritic spines on cortical pyramidal neurons, increased basal protein synthesis in the hippocampus, exaggerated inhibitory avoidance extinction, audiogenic seizures and accelerated body growth. However, macroorchidism was not rescued. This work is supportive of the proposal by Bear et al. [146]that excessive mGluR5 signaling is responsible for the psychiatric and neurological symptoms of FXS, including cognitive deficits, seizures, anxiety, perseverative movements and social deficits.

Use of mGluR5 antagonists in animal models of FXS further supports the mGluR theory. MPEP (2-methyl-6-phenylethynyl pyridine hydrochloride) is a potent, highly selective antagonist of mGluR5 receptors [147]. In vitro, both MPEP and fenobam, another mGluR5 antagonist, were able to rescue hippocampal dendritic abnormalities in the KO mice [148,149]. MPEP has reversed audiogenic seizures, epileptiform discharges, open field hyperactivity and the defect in prepulse inhibition (PPI) of the startle response in KO mice [148-150]. When MPEP and lithium, a partial mGluR5 antagonist that also blocks GSK3β, were given to dfmr1 loss of function Drosophila mutants, the flies had restored normal courtship behavior, memory and brain structural abnormalities through the reduction of mGluR activity [151]. MPEP is toxic to humans, so other mGluR5 antagonists including fenobam have been studied in FXS [152,153]. Fenobam was found to be safe in a single dose trial in 12 adults with FXS. There were improvements in hyperactivity and anxiety, and 50% showed at least a 20% improvement in PPI [152]. Currently there are two additional mGluR5 antagonists undergoing trials in adults with FXS at multiple centers [153].

Other mechanisms to downregulate glutamate release and modulate mGluR overactivity have been investigated. γ Aminobutyric acid (GABA)B receptor agonists, such as baclofen, inhibit both presynaptic release of glutamate and postsynaptic transmission and/or intracellular signaling downstream from mGluR5 [154-156]. Baclofen has been shown to be efficacious in treating hyperactivity [157], marble burying (Seaside Therapeutics, unpublished data) and audiogenic seizure phenotypes in FX KO mice [158]. A double-blind, placebo-controlled, crossover trial of arbaclofen, the right sided isomer of baclofen that is significantly more potent than regular baclofen as a GABA agent, has just been completed at multiple centers,and involved over 60 individuals with FXS (aged 6 years and older). The preliminary safety and efficacy results are positive, with improvement in the Clinical Global Impression Improvement scale in those with the most severe baseline ratings [159]. There are also preliminary studies that are taking place involving individuals with autism without FXS, and these studies have also produced preliminary positive results. Therefore, further studies on both FXS and autism are set to take place.

The GABAergic system is also dysregulated in FXS, and GABA agents are important to consider for targeted treatment studies in FXS. GABA is a major inhibitory neurotransmitter receptor in the brain, which is important in anxiety, depression, epilepsy, insomnia, and learning and memory [160]. GABA-mediated inhibition is important for terminating ictal discharges and the spread of hyperexcitability, which can lead to seizures [161].

There are two main subtypes of GABA receptors: GABAA and GABAB. The main difference between them is that the first is a ligand gated Cl- channel that gives fast inhibition, whereas the latter is a G-protein coupled receptor which gives slower and more prolonged inhibitory signals [162,163]. The metabotropic GABAB receptor can either be presynaptic and inhibit the release of neurotransmitters through downregulation of high-voltage activated Ca2+-channels; or, when postsynaptic, decrease neuronal excitability through its influence on K+ channels. Thus, GABAB agonists such as arbaclofen mediate their downregulating effects on either side of the synapse. The ionotropic GABAA receptor is usually localized postsynaptically, and their activation leads to opening of Cl- channels and hyperpolarization of the membrane potential, thus making it difficult for excitatory neurotransmitters such as glutamate to generate an action potential. GABAA receptors are more abundant than GABAB receptors in mammalian brain, and disorders such as epilepsy, sleep disorders and anxiety are now being treated using drugs that act on the GABAA receptor[164].

Direct binding between FMRP and the mRNA of the delta subunit of the GABAA receptor has been shown [165]. Reduced expression and dysfunction of several subunits of the GABAA receptor (α1, α3, α4; β1, β2; γ1, γ2 and δ) have been shown in FX animal models [166-168]. FMR1 Drosophila mutants destined to die from glutamate toxicity were rescued after administering molecules involved in the GABAergic pathway [166]. In addition, abnormal male courtship behavior and mushroom body abnormalities were rescued by GABA agents [166].

There is a profound reorganization of neocortical inhibitory circuits of GABAergic intraneurons in the KO mouse [164,167-173]. Recent evidence indicates that deficits in GABA-mediated inhibition may underlie many of the key symptoms in FXS, including the seizures, anxiety and autistic-like behaviors [167,169,173]. The neocortex in KO mice exhibits a marked reduction in the density of GABAergic interneurons that stain with parvalbumin. Moreover, electrophysiological studies in brain slices from these animals exhibit impaired GABAA receptor-mediated inhibitory function [174]. In addition to a gross reduction in GABA-mediated inhibition caused by the maldevelopment of inhibitory circuits and the loss of GABAergic interneurons, there is also evidence of altered GABAA receptor subunit expression in the FX KO mouse [167]. In particular, there appears to be a selective reduction in the expression of δ subunits [167,168]. Global expression analysis by means of the differential display in the FX mouse model revealed consistent underexpression of only three genes, one of which was the GABAA receptor subunit δ. As GABAA receptors are the major inhibitory receptors in the brain, and are specifically involved in processes that are disturbed in FX, including neuronal excitability (leading to enhanced seizure susceptibility), anxiety, sleep and learning, enhancement of the function of GABAA receptors may have major therapeutic benefits for FXS. Kooy and colleagues [175] have demonstrated that use of the GABAA agonist ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one) improved seizures in the KO mouse model of FXS. Ganaxolone is a 3β-methylated synthetic analog of the progesterone metabolite allopregnanolone, which is itself a neuroactive steroid. Unlike progesterone, neither allopregnanolone nor ganaxolone have direct hormonal activity via progesterone receptor activation, and cannot cause hormonal side-effects. However, allopregnanolone and ganaxolone are powerful positive allosteric modulators of GABAA receptors [161]. Human trials indicate that ganaxolone is well tolerated and that it may be efficacious in the treatment of diverse forms of epilepsy in children and adults [176-180]. Plans for studies on ganaxolone are currently underway in children and adults with FXS.

Minocycline, a widely used antibiotic used to treat acne and skin infections, is another promising drug that may target core symptoms of FXS and autism. Minocycline inhibits matrix metalloproteinase (MMP)-9 and reduces inflammation in the central nervous system. MMPs are enzymes involved in synaptic plasticity, and are associated with immature dendritic spine morphology [140,181]; MMP-9 is elevated in FXS. When minocycline was administered to FMR1 KO mice, their hippocampal neurons exhibited mature dendritic spines, and behaviorally, they showed decreased anxiety and improved exploration skills [140]. Off-label use of minocycline to treat 50 individuals with FXS resulted in two-thirds of families noticing positive improvements in their child’s language, attention and/or behavioral improvements while on the medication [182]. An open-label trial is ongoing to investigate the effects of minocycline on children with regressive autism at the National Institute of Mental Health (NIMH). Paribello reported beneficial effects on the CGI and the Aberrant Behavior checklist in an open trial of minocycline involving patients with FXS who were aged 13 and older [183]. Currently, a double-blind, placebo-controlled clinical trial is in progress at the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute for individuals with FXS who are aged 3.5 to 16 years

FXS has led the way for targeted treatments in neurodevelopmental disorders, and many of the treatments guided by molecular abnormalities in FXS may also be helpful for non-FX autism. The treatment trials will now combine targeted treatments, which strengthen synaptic connections, with enhanced educational and behavioral interventions to further develop appropriate synaptic connections in FXS. These targeted treatments combined with educational interventions look promising for reversing the intellectual and behavioral problems of FXS. Because of the shared neurobiological and molecular pathways, these interventions will hopefully also prove helpful in a subset of patients with idiopathic autism

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Conclusions

FX syndrome and autism are intertwined, because FMRP regulates the translation of many messages that affect synaptic plasticity and connectivity in the central nervous system. The absence of FMRP also leads to upregulation of mGluR5 pathways and downregulation of GABAA pathways. Targeted treatments to reverse these problems are currently being studied in patients with FXS. Many of these targeted treatments may also be helpful for ASD without FXS.

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Closing in on targeted treatments for fragile X

UC Davis Health System, march 16 |

Maude Brownlie, who lives in Melrose, Scotland, wasn’t aware of her head tremors until her young granddaughter pointed it out. Over the next few years, the tremors worsened and spread, causing balance problems that resulted in several falls and phantom pains. She also began losing her words. A dynamic woman who adored being a grandmother, she became irritated, fatigued and depressed by her physical and cognitive decline.

Disheartened by the lack of information from her own physicians, Brownlie sought answers. Her daughter, whose sons had been diagnosed with fragile X syndrome, suggested she meet with the team at the MIND Institute at UC Davis Health System.

Randi Hagerman, medical director of the MIND Institute, discovered that Brownlie was a carrier of the premutation of fragile X. She diagnosed Brownlie with fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition that was causing her symptoms.

“I was very much against going and felt that it would be a complete waste of their time and our money,” she says. “How wrong I was!”

Fragile X is a family of genetic conditions that includes FXTAS, which Hagerman and her fellow researcher and husband, Paul, a molecular biology physician-scientist and director of the Neuro- Therapeutics Research Institute, discovered in 2001. It also includes fragile X syndrome (FXS), the most common cause of inherited intellectual disability and the most common known single-gene cause of autism, and fragile X-associated primary ovarian insufficiency (FXPOI), a problem with ovarian function that can lead to infertility and early menopause.

Brownlie and her family had consulted with the right team. Researchers at the MIND Institute are at the epicenter of robust basic and translational science research into psychopharmacological treatments for FXS and FXTAS.

“This is a most exciting time for us,” says Randi Hagerman, also the co-founder of the world-renowned National Fragile X Foundation. “Our goal is to reverse the neurobiological, structural and hopefully cognitive and behavioral abnormalities of fragile X.”

One in 129 women is estimated to carry the fragile X premutation. Like Brownlie, women typically show no neurodevelopmental deficits in youth. One in 3,600 individuals has the full mutation, which results in fragile X syndrome. Approximately one-third of all children diagnosed with FXS have autism and another third have some features of autism spectrum disorder (ASD).

The treatments in trial for FXS are designed to address the core of the genetic problem: the absence or deficiency of a single protein, the fragile X mental retardation protein (FMRP).

FMRP is a “mother protein” that controls the translation of about 800 genetic messages, many of which are important for synaptic plasticity. With fragile X syndrome, this protein is eliminated or deficient, thus interfering with normal brain development and learning.

One affected system, for example, is the metabotropic glutamate receptor 5 system (mGluR5), an excitatory system that leads to the weakening of synaptic connections. In a regularly functioning system, FMRP works something like a gatekeeper to keep mGluR5 activity in check. In the absence of FMRP, the gate is left open, and enhanced activity leads to weak synaptic connections throughout the brain. This leads to anxiety, hyperactivity, impulsivity, a short attention span and social deficits that can include autism.

In a pilot study reported in the Journal of Medical Genetics, researchers at the MIND Institute and Rush University Medical Center, Chicago, found that an mGluR5 antagonist called fenobam helped to lower mGluR5 activity, which calmed behavior and reduced hyperactivity and anxiety in patients with FXS. The New York Times reported in April 2010 that another antagonist was successfully used in a European medical trial. The principal investigators of that study were trainees from the MIND Institute: Sebastien Jacquemont and Vincent Des Portes.

The remarkable promise of mGluR5 antagonists is spurring further research. The MIND Institute has three additional clinical trials scheduled throughout 2010 and 2011.

Two pharmaceutical treatments that show particular promise for younger patients are arbaclofen and minocycline. A controlled trial of arbaclofen in children and adults with FXS was completed in April 2010, and preliminary positive results were presented at the 2010 International Meeting for Autism Research. A six-month double-blind controlled trial of minocycline, funded by the National Fragile X Foundation, began in February 2010 and studies children ranging in age from 3.5 years to 16 years.

Also under way is a study of memantine, a medication used to treat moderate to severe Alzheimer’s disease. The study is funded by the National Institutes of Health for people with the fragile X premutation who have FXTAS – like Brownlie. FXTAS is of special interest because it reveals a generational gap that the Hagermans uncovered.

“Current research on FXS and autism has led to dramatic advances in understanding aging and even dementia,” Randi Hagerman explains. “We now know the premutation can cause problems in adult life, including depression, anxiety, mood instability, early cognitive decline, difficulties with ovarian failure and FXTAS. It’s all related.” Brownlie found relief with a treatment regimen of memantine and an antidepressant. When she returned to the MIND Institute for an annual evaluation, her tremors had been greatly reduced and her depression was gone.

“She was a completely changed woman,” Hagerman says.

“My experience with the MIND Institute and UC Davis has had a hugely beneficial outcome,” Brownlie says. “I am really enjoying … my ‘new self.’ My energy levels, self-esteem and confidence are back to what they were five years ago. My aim now is to persuade the other FX carriers in my family to be assessed by the team at the MIND Institute. Or, just maybe, some interested professionals in the U.K. will come on board and extend the research so that treatment is available here.”

“Our team is on the cusp of finding effective drugs to mitigate fragile X syndrome’s devastating impact,” Hagerman says, “and we are leading the way to restoring quality of life for all generations of families affected by fragile X.”

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Neuroscience drug discovery center opens at Vanderbilt

by Bill Snyder | Posted on Friday, Mar. 11, 2011 — 2:55 PM

(…) With Seaside Therapeutics in Cambridge, Mass., the team is trying to “tune down” excessive signaling through two different pathways. The goal is to relieve – for the first time with a drug – learning, memory, social and behavioral problems associated with Fragile X syndrome, the most common inherited form of mental retardation and the most common genetic cause of autism. (…)

‘Mice that model fragile X syndrome have trouble changing their minds…’

Jessica Wright, Sfari.org |

Mice that model fragile X syndrome have trouble changing their minds, according to a study published in the Proceedings of the National Academy of Sciences in February. This behavior is accompanied by fewer connections between neurons in the prefrontal cortex — a brain region involved in higher-level cognition, such as decision-making.

Fragile X syndrome is a disorder that has some overlap with autism and includes defects in mental flexibility, such as the inability to respond to changing conditions or to shift attention. The prefrontal cortex regulates these processes and is likely to play an important role in the disorder.

Mice lacking the fragile X mental retardation gene FMR1 show deficits in behaviors controlled by the prefrontal cortex, according to the study. These mice learn easily that poking their noses into any of five holes leads to a food reward, but they take much longer than control mice do to adjust when only the hole accompanied by a blinking light gives out a reward.

Fragile X mice also appear to have a favorite hole: they show a strong preference for a certain hole even once it stops giving out food.

The same mice also have lower levels in the prefrontal cortex of several proteins that help transmit neuronal signals — including those encoded by the autism-associated gene NR2A, also known as GRIN2A, and the Williams syndrome gene PSD-95.

Levels of NR2A are lower in the prefrontal cortex of mice that take longer to adjust in the hole test, suggesting a direct correlation between this protein and the behavioral deficits.

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mGluR5 inhibition and Fragile X syndrome, pain, anxiety, depression and gastroesophageal reflux disease (GERD)

Addexpharma.com |

Dipraglurant (ADX48621) is a negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5). This mechanism has been clinically validated and has blockbuster potential in several indications, including: anxiety; gastroesophageal reflux disease (GERD); acute treatment of migraine; Fragile X syndrome; Parkinson’s disease levodopa-induced dyskinesia (PD-LID); and nonparkinsonian dystonias, like idiopathic torsion dystonia (ITD, also early-onset generalized dystonia) and cervical dystonia (spasmodic torticollis).

PD-LID and dystonia have been chosen as the lead indications because preclinical data indicate that dipraglurant may be particularly well suited for these indications. Specifically, dipraglurant is the first drugcandidate in preclinical testing reported to reduce both of the major PD-LID symptoms, chorea (rapid uncontrolled movements) and dystonia (writhing and cramping movements). While dystonia is a significant problem for PD patients, dytonias also occur as a variety of separate conditions of either primary (e.g. hereditary) or secondary (drug-induced or otherwise acquired) origin. There are currently no products specifically licensed for treatment of dystonias and there is a large unmet medical need with substantial commercial potential for an effective product in this indication. This differentiation may ultimately mean that dipraglurant could become the best-in-class product for PD-LID and one of the first meaningful treatments for dystonia.

Because of its unique properties (and their long standing interest in the mGluR5 NAM mechanism) The Michael J. Fox Foundation for Parkinson’s Research awarded a USD900,000 grant to Addex to support the Phase IIa PD-LID trial of dipraglurant in September 2010. The foundation, which involves some of the world’s leading Parkinson’s researchers via its scientific advisory board, is known for actively supporting cutting edge research and products.

An immediate release formulation of dipraglurant, dipraglurant-IR, will enter Phase IIa clinical testing in patients with PD-LID in the first half of 2011.

Development of an extended-release formulation of dipraglurant was performed in 2010 and Phase I testing of dipraglurant-ER will commence mid-2011. Dipraglurant-ER has been developed for clinical testing for treatment of non- Parkinsonian dystonia and potentially by a licensee for other indications, including Fragile X syndrome, pain, anxiety, depression and gastroesophageal reflux disease (GERD), all of which have validation. A Phase IIa study of dipraglurant- ER for the treatment of non-Parkinsonian dystonias, is scheduled to start in 2012.

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Maladies rares : les médecins très mal (in)formés

Doctissimo.fr |

Les patients atteints de maladies rares sont souvent confrontés à une errance diagnostique, en partie liée à un manque d’informations des professionnels de santé. Pour réduire les inégalités de soins qui en découlent, un effort à destination des médecins apparaît primordial.

(…) Cette méconnaissance des maladies rares est à l’origine même de l’errance diagnostique dont sont victimes la plupart des patients, errance qui est de 8 ans en moyenne pour le syndrome de l’X fragile

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L’X fragile sur M6 | Santé : Vincent, 16 ans, “X fragile”

Santé : Vincent, 16 ans, “X fragile”…
On compte jusqu’à 8.000 maladies rares. Des maladies dont les noms sont parfois très énigmatiques tel que le syndrome de l’X fragile, qui touche en majorité des garçons. Parmi eux : Vincent, 16 ans, qui, malgré le handicap, s’accroche à son rêve…
Vidéo ici

Left behind

Deborah Rudacille, Sfari.org |

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Meanwhile, a survey exploring the lives of 328 men and women with fragile X syndrome found that those who have both fragile X and autism have less independence than those with fragile X alone. The most common leisure activities among both men and women with fragile X syndrome are watching television, playing video games and listening to music — all solitary in nature, the researchers note.

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Genetic background alters behavior of fragile X mice

Deborah Rudacille, Sfari.org |

Six strains of mice lacking a gene associated with fragile X syndrome show radically different behaviors though they share the same mutation, researchers reported in January in Autism Research1.

 

Fragile X syndrome is caused by the complete or partial loss of FMR protein, which results from a full or partial mutation of theFMR1 gene. People with the syndrome combine varying degrees of intellectual disability with seizures, irritability, hyperactivity, anxiety or self-injurious behavior. Up to one-half of people with fragile X syndrome also meet diagnostic criteria for autism.

Researchers suspect that the wide range of fragile X symptoms is the result of differences in genetic, environmental and perhaps epigenetic factors — which affect gene expression without altering DNA2.

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US | HARPER, ENGEL REESTABLISH HOUSE FRAGILE X CAUCUS

February 14, 2011

HARPER, ENGEL REESTABLISH HOUSE FRAGILE X CAUCUS

WASHINGTON, DC – U.S. Representatives Gregg Harper (R–Miss) and Eliot Engel (D–NY) today announced the reinstatement of the Congressional Fragile X Caucus in the U.S. House of Representatives. The gentlemen will serve as the panel’s top Republican and Democratic members, respectively.

The bipartisan caucus is committed to increasing awareness of Fragile X-associated Disorders and improving the health of children and adults across the country living with this intellectual disability. Fragile X-associated Disorders are genetic – resulting in behavioral, developmental and language disabilities throughout a person’s lifespan.

“As the parent of a 21-year-old son with Fragile X Syndrome, I understand fully the daily challenges faced by families with special needs children,” said Harper. “For our family, Fragile X has become a lifelong labor of love and daily blessings.”

“Fragile X syndrome is perhaps the most common cause of inherited mental impairment,” added Engel. “I am eager to serve as co-chair of this Congressional Caucus, with my friend and colleague Rep. Harper, to bring this issue before the public and strive to enhance public and private abilities to advance our knowledge of this syndrome. The striking rise of autism is reason enough for this Caucus to exist but there are other conditions caused by this genetic disorder and we must do what we can to help the people with Fragile X syndrome and their families.”

For Fiscal Year 2011, the caucus – in close cooperation with the National Fragile X Foundation (NFXF) – reached many of its targeted objectives. The group worked with Members of Congress to push the National Institutes of Health (NIH) Research Plan on Fragile X Syndrome and Associated Disorders and urged Congress to continue providing resources for translational research that shows significant promise of a safe and effective treatment for this disability.

The panel also requested that the Department of Defense (DOD) expand the Peer Reviewed Medical Research Program to include Fragile X-associated Disorders in the eligible research topics for Fiscal Year 2011. Additionally, the Caucus advocated for sustained support to grow the National Fragile X Public Health Initiative and the Fragile X Clinical & Research Consortium in order to expand to geographically underserved regions.

“These accomplishments have had a significant impact on the Fragile X community, but this is only the beginning of Fragile X advocates’ promising journey,” added the chairmen. “We will maintain our efforts to ensure that every youth with a significant disability has the opportunity, encouragement and support to become gainfully employed in an integrated setting, pursue a post-secondary education, and contribute to and meaningfully engage in typical community settings upon leaving high school.”

Fragile X-associated Disorders are linked to a mutation on the X chromosome, and are the most commonly inherited form of intellectual disabilities. Fragile X is also connected to reproductive problems in women – including early menopause and a Parkinson’s-like condition in older male carriers.

Today, over 100,000 Americans live with Fragile X Syndrome and over one-million Americans carry a Fragile X mutation and either have, or are at risk for developing a Fragile X-associated Disorder. As many as one in 130 women are estimated to be carriers of the Fragile X mutation according to current studies.

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