080210xf's Blog

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

Archive for August, 2010

Matthew’s liberation – Seaside at forefront of new approach to Fragile X

By Karen Weintraub Globe Correspondent

It was the week the medication didn’t work that convinced Melissa Zolecki. She thinks her son Matthew got a bottle of inactive dummy pills that week by accident. And the change in his behavior was striking.

He was back to banging his head against the wall. He struggled to concentrate again at school. Then, there was the epic temper tantrum at Costco, normally one of his favorite places. Even the temptation of a hot dog didn’t help.

Matthew, 9, was out of control in a way he hadn’t been since starting an experimental drug eight months earlier.

Matthew has Fragile X, a rare genetic disorder that leaves 1 in 4,000 boys and 1 in 8,000 girls with intellectual deficits, severe anxiety, and behavioral problems often diagnosed as autism. There is no cure. The only treatment for Fragile X, as with autism, has been extensive behavioral therapy and drugs developed for other purposes such as schizophrenia, depression, and panic attacks.

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Fragile X protein linked to potassium channels

SFARI, Virginia Hughes, 24 August 2010

Mouse models of fragile X syndrome show defects in two kinds of potassium channels — ubiquitous pores that control the flow of electrical current across neurons — in a brain area that processes sound, according to two papers published this summer.

The syndrome results from the absence of the fragile X mental retardation protein, or FMRP, often leading to mental retardation, delayed speech and autism. Although it is a little-studied phenomenon, anecdotal reports have shown that many people with fragile X syndrome are particularly sensitive to loud sounds1 and have fluctuations in their speech2. An estimated one in four people with the syndrome are also prone to epilepsy3.

The new studies suggest that unchecked signals from potassium channels could explain why people with the disorder have trouble filtering a barrage of auditory information.

“[The work] is the first to really look at the molecular and cellular basis of this auditory defect — that’s one reason that it’s a breakthrough,” notes Suzanne Zukin, professor of neuroscience at Albert Einstein School of Medicine, who was not involved in the studies.

Another reason, she says, is that the findings might help researchers develop treatments, based on existing drugs that target potassium channels, to improve these problems.

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Matthew’s liberation Seaside at forefront of new approach to Fragile X

By Karen Weintraub Globe Correspondent / August 23, 2010

It was the week the medication didn’t work that convinced Melissa Zolecki. She thinks her son Matthew got a bottle of inactive dummy pills that week by accident. And the change in his behavior was striking.

He was back to banging his head against the wall. He struggled to concentrate again at school. Then, there was the epic temper tantrum at Costco, normally one of his favorite places. Even the temptation of a hot dog didn’t help.

Matthew, 9, was out of control in a way he hadn’t been since starting an experimental drug eight months earlier.

Matthew has Fragile X, a rare genetic disorder that leaves 1 in 4,000 boys and 1 in 8,000 girls with intellectual deficits, severe anxiety, and behavioral problems often diagnosed as autism. There is no cure. The only treatment for Fragile X, as with autism, has been extensive behavioral therapy and drugs developed for other purposes such as schizophrenia, depression, and panic attacks.

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New Drug Strategy Against Fragile X Syndrome Identified

by Kathy Jones |

A potential new strategy for treating fragile X syndrome, the most common inherited cause of intellectual disability has been identified by researchers at Emory University School of Medicine.

The researchers have found that a class of drugs called phosphoinositide-3 (PI3) kinase inhibitors can correct defects in the anatomy of neurons seen in a mouse model of fragile X syndrome. In experiments with cultured neurons from the hippocampus, a brain region involved in learning and memory, the drugs could restore normal appearance and levels of protein production at synapses, the junctions between cells where chemical communication occurs. The results, published online this week in the Journal of Neuroscience, suggest that PI3 kinase inhibitors could help improve learning and cognition in individuals with fragile X syndrome.

“This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,” says senior author Gary Bassell, professor of cell biology and neurology at Emory University School of Medicine. He adds that his group has recently begun experiments in the mouse model to assess PI3 kinase inhibitors’ effects on behaviors associated with fragile X syndrome.

New drug strategy against fragile X

emoryhealthsciblog.com

Even as clinical trials examining potential treatments for fragile X syndrome gain momentum, Emory scientists have identified a new strategy for treating the neurodevelopmental disorder.
In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.

“This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,” he says.

A recent Nature Biotechnology article describes pharmaceutical approaches to autism and fragile X.

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Parents of children with autism: We struggle alone – KansasCity.com

… For families with children with autism spectrum disorders – a range of developmental disabilities that cause social, communication and behavioral problems – each day can be emotionally overwhelming, stress-filled and isolating.

Family and friends shy away. The child’s behavior can leave parents prisoners, trapped at home. If they venture out, passers-by stare, wondering why the child isn’t under control.

“Sometimes, the parents think they’re admitting failure when they ask for help,” said Shanel Tarrant-Simone, the single mother of twin 10-year-old autistic sons. “‘I’m the parent; I should know how to deal with it.’

“But no parent is equipped to do this.”

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Brain’s adaptability begins at single synapse

SFARI, Kelly Rae Chi

Researchers have uncovered an important molecular piece of a learning mechanism that occurs at the junction between neurons. The findings, which may help understand how the brain is disrupted in disorders such as autism, appear in the 24 June issue of Neuron1.

Disruptions in synaptic plasticity — the ability of synapses, the connections between neurons, to change in strength — have long been linked to autism and related disorders, such as fragile X syndrome. But much less is known about ‘metaplasticity,’ the degree to which synaptic plasticity itself can strengthen or weaken.

Researchers believe that metaplasticity is controlled by molecular changes occurring in entire neurons and networks. Although its exact mechanisms are still unclear, the new study shows for the first time that it can also occur at a single synapse.

Without metaplasticity, neuronal activity would go haywire during early development. Strong synapses would strengthen at a constant rate, making them less sensitive to stimulation, and weak synapses would get steadily weaker until they are eliminated. Tweaks to the levels of plasticity prevent these situations, creating stable yet flexible circuits that allow the brain to adjust to changes in the environment and learn new things.

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Fragile X models give clues to stem cell programming

SFARI, Virginia Hughes

Not all stem cells are created equal, a string of new studies suggests: adult cells that are reprogrammed into stem cells carry chemical remnants of the tissue from which they originate, making them distinct from embryonic stem cells. These differences may have important implications for studying fragile X syndrome and other diseases that arise from epigenetic glitches.

Embryonic stem (ES) cells can be derived from human embryos, and have the potential to give rise to any type of cell in the body. Induced pluripotent stem (iPS) cells are, in contrast, created in the lab by placing adult cells — typically skin, muscle or blood — in a soup of chemicals, and reversing them into an undifferentiated state.

When a Japanese team first debuted iPS cells in 2006, many researchers became hopeful that the cells could be used to model diseases just as well as their polemical counterparts, ES cells. Several groups are using iPS cell models to screen drugs for various diseases.

Two reports published on 19 July, however, found that iPS cells in mice are not in a fully reset state1,2. Rather, these reprogrammed cells retain epigenetic markers — chemical add-ons to DNA — of the differentiated tissue from which they originate.

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