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A means for autistic people to restore correct interpretation of sensory information

In autistic children, information coming from the 5 senses – touch, hearing, sight or other stimuli – are not correctly interpreted in the brain, leading to inappropriate behaviour and sometimes uncontrollable reactions. Inserm researchers led by Andréas Frick in Inserm Unit 862 ‘Magendie Neurocentre’ have recently understood why by studying a mouse model mimicking the disorder. They have even found a molecule that could reverse these effects and restore ‘normal’ behaviour in these mice.

These findings are published in the journal Nature Neuroscience

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Autistic Spectrum Disorders (ASD) affect more than 3 million people in the European Union, including about 650,000 in France. Recent estimates from the Centre for Disease Control (in the USA) suggest that one child in 68 is affected by this disorder. ASDs are neuro-developmental disorders that affect children from all ethnic and socio-economic origins, and are characterised by a spectrum of symptoms including both difficulties in social interactions and communication as well as stereotypical repetitive behaviours.

Another common aspect of neuro-developmental disorders is the problem of processing sensory information. Nearly 90% of children with ASDs are affected by different types of sensory problems. Problems of sensory interpretation derive from the fact that peripheral information, whether from touch, hearing, sight or other stimuli, are not interpreted or organised correctly in the brain, leading to inappropriate behaviour. Such problems can be extremely disabling in daily life for people affected by autism and they create a challenge for parents and teachers. For example, during a visit to the supermarket, simple fluorescent lights can be an unpleasant sensory experience. Unfortunately, alterations of sensory interpretation in these disorders and their pharmacological treatments are little studied, even if these alterations are also frequently observed in a related neuro-developmental disorder, Fragile X Syndrome.

In a study published in Nature Neuroscience, Inserm researchers (working with researchers from the French CNRS – national centre for scientific research) have shown that Fragile X mice display disorders in the manner that sensory information is processed by the neocortex, which is one of the parts of the brain responsible for sensory perception. The researchers have shown that the neocortex of these mice is hyperexcited in response to tactile sensory stimulation. They then performed a variety of detailed tests showing that this neocortical hyperexcitability is linked to the way the neurons in this region of the brain interpret sensory information. With this study, the researchers found that the function of certain ionic channels (molecules that determine the manner in which neurons process electrical signals) is altered in the dendritic compartment (the structure that interprets information and really behaves as the ‘brain’ of neurons).

By using a pharmacological molecule mimicking the function of one of these channels, they were able to correct this neocortical hyperexcitability as well as the neuron interpretation anomalies.

Furthermore, they were also able to correct a behavioural consequence, particularly of hypersensitivity to sensory stimuli (healthy mice were not affected by this treatment). These findings offer new hope for personalised treatment for the sensory aspects of Fragile X Syndrome and autistic spectrum disorders, especially because these treatments could be applied to adult or adolescent patients.

Production of human motor neurons from stem cells is gaining speed

The motor neurons that innervate muscle fibres are essential for motor activity. Their degeneration in many diseases causes paralysis and often death among patients. Researchers at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases (I-Stem – Inserm/AFM/UEVE), in collaboration with CNRS and Paris Descartes University, have recently developed a new approach to better control the differentiation of human pluripotent stem cells, and thus produce different populations of motor neurons from these cells in only 14 days. This discovery, published in Nature Biotechnology, will make it possible to expand the production process for these neurons, leading to more rapid progress in understanding diseases of the motor system, such as infantile spinal amyotrophy or amyotrophic lateral sclerosis (ALS).



Human pluripotent stem cells have the ability to give rise to every cell in the body. To understand and control their potential for differentiation in vitro is to offer unprecedented opportunities for regenerative medicine and for advancing the study of physiopathological mechanisms and the quest for therapeutic strategies. However, the development and realisation of these clinical applications is often limited by the inability to obtain specialised cells such as motor neurons from human pluripotent stem cells in an efficient and targeted manner. This inefficiency is partly due to a poor understanding of the molecular mechanisms controlling the differentiation of these cells.

Inserm researchers at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases (I-Stem – Inserm/French Muscular Dystrophy Association [AFM]/University of Évry Val d’Essonne [UEVE]), in collaboration with CNRS and Paris-Descartes University, have developed an innovative approach to study the differentiation of human stem cells and thus produce many types of cells in an optimal manner.

“The targeted differentiation of human pluripotent stem cells is often a long and rather inefficient process. This is the case when obtaining motor neurons, although these are affected in many diseases. Today, we obtain these neurons with our approach in only 14 days, nearly twice as fast as before, and with a homogeneity rarely achieved,” explains Cécile Martinat, an Inserm Research Fellow at I-Stem.

To achieve this result, the researchers studied the interactions between some molecules that control embryonic development. These studies have made it possible to both better understand the mechanisms governing the generation of these neurons during development, and develop an optimal “recipe” for producing them efficiently and rapidly.

“We are now able to produce and hence study different populations of neurons affected to various degrees in diseases that cause the degeneration of motor neurons. We plan to study why some neurons are affected and why others are preserved,” adds Stéphane Nedelec, an Inserm researcher in Cécile Martinat’s team.

In the medium term, the approach should contribute to the development of treatments for paralytic diseases such as infantile spinal muscular amyotrophy or amyotrophic lateral sclerosis. “Rapid access to large quantities of neurons will be useful for testing a significant number of pharmacological drugs in order to identify those capable of preventing the death of motor neurons,” concludes Cécile Martinat.

These results are the subject of a patent application with Inserm Transfert.

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