Effective non-invasive ultrasound therapy in the treatment of heart valve diseases

cœur© Adobe stock

Currently, the treatment of heart valve diseases relies on the replacement of the dysfunctional valve with an artificial prosthesis. However, this procedure cannot be offered to all patients due to its invasive nature. In a new study, a group of researchers from laboratories shared by Inserm, ESPCI Paris, CNRS and Université Paris Cité, in close collaboration with the start-up Cardiawave[1] spin-off of the Georges Pompidou European Hospital and the Paris Medical Physics Laboratory (Inserm/CNRS/ESPCI/PSL), report for the first time the clinical efficacy of a “non-invasive” focused ultrasound therapy. The clinical trial, conducted on a sample of 40 patients, significantly improved their health. Their findings have been published in The Lancet.

Our heart beats about 70 times a minute at rest, or more than 100,000 times a day. It pumps blood into the body at a rate of 4 to 5 litres per minute. This is why with age the heart ages, arteries and valves can become damaged[1]. More than 10 million people have calcified aortic stenosis (CAR) in Europe and the United States, including 2 million severe cases, particularly in the elderly. In this disease, the aortic valve (positioned between the heart pump and the vascular system) calcifies, becomes rigid and can no longer open properly, leading to heart failure or sudden death. Today, the only existing treatment consists of the replacement of the defective valve with an artificial prosthesis, by open heart surgery via percutaneous arterial surgery. However, a significant number of patients are not eligible for these invasive procedures due to severe comorbidities and limited life expectancy.

Finding a therapeutic alternative for these patients is a major challenge for research. For example, a research team from Inserm’s French academic laboratories has developed and tested a new approach called “non-invasive ultrasound therapy” (or NIUT). After validating the concept, the technology was developed by Cardiawave, a spin-off start-up from a collaboration between the Georges-Pompidou European Hospital (AP-HP) and laboratories shared by Inserm, ESPCI and the CNRS (Paris Physical Institute for Medicine and Langevin Institute).

This approach is based on a technology that makes it possible to repair the aortic valve thanks to the precise and mechanical action of high-energy focused ultrasound delivered by a device applied to the patient’s chest, with the aim of softening the valve and thus improving its opening.

A clinical trial was conducted on a sample of 40 patients with severe forms of the disease at three clinical sites in France (Hôpital Européen Georges-Pompidou, AP-HP, Paris), the Netherlands (Hôpital Amphia, Breda) and Serbia (Centre clinique universitaire de Serbie, Belgrade). They were treated in a single session, with follow-ups scheduled at 1, 3, 6, 12 and 24 months.

At the end of the follow-up, the scientists observed:

  • no death or serious events (infarction, stroke, severe rhythm disorders) related to the procedure;
  • a significant improvement in cardiac function (confirmed as early as 6 months after treatment with the device, reflected in particular by a 10% increase in the mean aortic valve surface area);
  • significant improvement in quality of life; improvement in heart failure symptoms[2]: physical capacity, shortness of breath on exertion. One of the tests consists, for example, of measuring the distance travelled by walking 6 minutes (6-minute walking test).

valve aortique

The aortic valve consists of several leaflets (3 most often) which, when they become calcified, prevent it from opening properly. After ultrasound treatment, we see a significant improvement in the opening surface of the aortic valve shown here in the image on the right.


These promising results represent a paradigm shift in the treatment of calcified aortic stenosis”, explains Emmanuel Messas, Principal Investigator of the clinical study.

“They show that this innovative approach is feasible and safe, and has significantly improved the hemodynamic and clinical parameters as well as the quality of life of the patients participating in the clinical trial,” adds Mickaël Tanter, Inserm Research Director at the Physics for Medicine laboratory in Paris.

“If its effectiveness is confirmed, this technology could represent immense hope for millions of patients suffering from severe forms of ORA who are currently at a therapeutic impasse,” explains Mathieu Pernot, Inserm Research Director at the Physics for Medicine laboratory.

The device called Valvosoft® is currently undergoing clinical safety and efficacy studies. It has not yet received marketing authorisation (CE marking, etc.) and is for the time being intended exclusively for clinical studies.

This project was supported by the Investments for the Future Program as part of the Global Innovation Competition. It also benefited from public aid managed by the French National Research Agency and the Horizon 2020 programme, the European Commission’s SME instruments.


[1]This study was led by Cardiawave, a spin-off start-up from Institut Langevin (Inserm/CNRS/ESPCI) and Physique for Medicine Paris (Inserm/CNRS/ESPCI/PSL)

[2]The New York Heart Association (NYHA) score for measuring the severity of heart failure improved or stabilized in 96% of patients (n=24); and the Kansas City Cardiomyopathy Questionnaire (KCCQ) mean score—another score for measuring the severity of heart failure—improved by 33%.

[3]The New York Heart Association (NYHA) score for measuring the severity of heart failure improved or stabilized in 96% of patients (n=24); and the Kansas City Cardiomyopathy Questionnaire (KCCQ) mean score—another score for measuring the severity of heart failure—improved by 33%.

A Surprising Discovery About the Pulse


The pulse wave is used in everyday life to check heart rate. © Adobe Stock


We are all familiar with taking our pulse to check our heart rate. This signal is due to the propagation of a wave caused by the arteries dilating under the surge of blood from the heart. While we thought we knew the pulse well, the latest research by an international team led by Inserm researcher Stefan Catheline at the Laboratory of Therapeutic Applications of Ultrasound (Inserm/Université Claude Bernard Lyon 1/Centre Léon Bérard) shows that this was not the case. Their findings, published in Science Advances, show that the arteries not only dilate but also twist under the effect of the blood flow. This phenomenon generates a second “flexural” wave which propagates much more slowly. While it ultimately provides information on the same parameters – heart rate and arterial elasticity – the unprecedented measurement of this wave adds to our knowledge of the pulse.

Since 1820, pulse wave has been used in everyday life to check the heart rate of an athlete or inanimate person, or to assess arterial health, for example. It corresponds to the dilatation of the arterial wall following the surge of blood caused by the heart’s contractions, which propagates in an undulating manner along the arteries throughout the body.

An international research team led by Stefan Catheline, Inserm researcher at the Laboratory of Therapeutic Applications of Ultrasound (Inserm/Université Claude Bernard Lyon 1/Centre Léon Bérard), has just shown that in reality there is not one pulse wave but two. In addition to the principal wave, which is well-known and felt when touching the carotid artery or base of the wrist, there is a second one, which is more discreet but easily observable on ultrasound: the “flexural wave”, which had never been described until now.


A Chance Finding

It was somewhat by chance that Catheline’s team made this discovery. Specializing in waves and ultrasound therapies, it had been asked to test an innovative tool to analyze the retina: laser Doppler holography. This consists of photographing the organ at high speed and in very fine resolution to observe what is happening, and particularly to follow the arteries in motion. The researchers who developed this tool wanted to know if it could be used to calculate the speed of propagation of the pulse wave in the retina. Catheline’s team not only managed to measure this wave – which circulates at around one meter per second – but also detected a second wave signal nearly one thousand times slower.

The principles of fundamental physics on wave circulation in tubes are what enabled the scientists to better understand this phenomenon. Along the arteries, the two wave types actually propagate in two ways under the effect of the passage of the blood. The first is symmetrical to the central axis of the vessel and is when the arterial walls dilate and increase in diameter. The second is asymmetrical and results from the tube twisting in a so-called “sinusoidal” manner.

“Imagine a snake that swallows a prey which slides down the digestive tract – with the snake undulating away at the same time,” explains Catheline.

Following this discovery, the research team performed new ultrasound pulse measurements along the carotid artery of individuals and found both waves.

“It took us less than one afternoon to confirm the finding. This second wave, called a ‘flexural wave’, is present on all the recordings and is not difficult to observe. If it has never been described, it is simply because no-one had been looking for it,” explains Catheline.



schéma onde de pouls

The most well-known pulse wave (dilatation wave) is caused by the walls symmetrically separating outwards from the central arterial axis under the effect of the blood surge. And the newly-discovered flexural wave is caused by the artery twisting from side to side of this axis. © Stefan Catheline


And the Clinical Applications?

The principal pulse wave is widely used in medicine and reflects an individual’s cardiovascular health. Its speed of propagation depends on the condition of the artery walls: the younger and more supple they are, the slower the speed – and vice versa with age, with rigid arteries being a risk factor for cardiovascular events. However, given the high propagation speed of this wave, it is necessary to measure it over several centimeters to obtain a reliable value.

“With the flexural wave that we are describing here, whose slow speed ranges from one tenth to one thousandth of a meter per second depending on the arterial diameter, it is easier to study the signal on very short fragments and with other types of equipment than ultrasound, especially X-ray and MRI, explains Catheline. One millimeter is sufficient to obtain an accurate value, for example, to assess the state of the arteries in the retina,” he explains.

The researcher sees a second advantage in using this flexural wave in the clinic: by continuing to propagate in the veins there where the principal pulse wave is no longer detectable due to the distance from the heart, it would also provide information on the rigidity of the venous wall. He specifies, however, that in order to make it a clinical tool, research is needed in humans in order to correlate propagation speed and wall elasticity, as had been done previously for the principal dilatation wave.

Restoring Vision Through a New Brain-Machine Interface: Sonogenetic Therapy

 thérapie sonogénétique

Sonogenetic therapy consists of genetically modifying certain neurons in order to activate them remotely by ultrasound. © Alexandre Dizeux/Physics for Medicine Paris

Restore vision using a combination of ultrasound and genetics? This is the goal of an international team led by Inserm research directors Mickael Tanter and Serge Picaud from Paris’ Physics for Medicine unit (ESPCI Paris/PSL Université/Inserm/CNRS) and Vision Institute (Sorbonne Université/Inserm/CNRS), respectively, in partnership with the Institute of Molecular and Clinical Ophthalmology in Basel. In a new study, they provide proof of concept of this so-called “sonogenetic” therapy in animals. This consists of genetically modifying certain neurons in order to activate them remotely by ultrasound. The results show that when used on rodent neurons sonogenetics can induce a behavioral response associated with light perception. This discovery makes it possible to envisage, in the longer term, an application in blind people with optic nerve atrophy. The study has been published in Nature Nanotechnology.

Sonogenetic therapy consists of genetically modifying certain neurons in order to activate them remotely by ultrasound. This technology had previously been tested in culture and the first in vivo tests did not enable the researchers to become aware of its therapeutic potential linked to its very high spatiotemporal resolution. The genetic modification in question consists of introducing the genetic code of a mechanosensitive ion channel into the cells. The neurons that express this channel can then be remotely activated by low-intensity ultrasound applied to the surface of the brain without the need for contact (see diagram below).

Ultrasound waves can access tissue deep down, such as in the visual cortex – even from the surface of the dura mater[1] that surrounds the brain – and target very specific areas. It is these waves that form the basis for high-resolution brain imaging or ultrasound technologies. In this case, they enable highly selective activation, because only those neurons carrying the mechanosensitive channel and targeted by the ultrasound beam are stimulated.

In a recent study, a team of researchers led by Inserm research directors Mickael Tanter and Serge Picaud tested the efficacy of this sonogenetic therapy in animals. The aim of this research is to provide a solution to restore vision to patients having lost the connection between their eyes and brain due to conditions such as glaucoma, diabetic retinopathy, or hereditary or dietary optic neuropathies.

Their findings show that sonogenetic stimulation of the visual cortex induces a behavioral response associated with light perception. The animal learns an associative behavior in which it seeks to drink as soon as it perceives light. Ultrasound stimulation of its visual cortex induces the same reflex, but only if the neurons in the cortex express the mechanosensitive channel. The animal’s behavior suggests that sonogenetic stimulation of its cortex induced the light perception at the origin of the behavioral reflex.

The study showed that therapy works on different types of neurons, whether in the retina or visual cortex of the rodents, thereby demonstrating the universal nature of this approach.

By converting the images of our environment into the form of a coded ultrasound wave to directly stimulate the visual cortex – at rates of several tens of images per second – sonogenetic therapy appears to offer genuine hope for restoring vision to patients who have lost optic nerve function.

More generally, this sonogenetic stimulation approach offers innovative technology for interrogating brain function. Unlike current neuron stimulators or prostheses, its “non-contact” and selective cell type functioning represents a major innovation in relation to electrode devices.

“This sonogenetic therapy to ultimately restore the vision of blind people illustrates the power of a multidisciplinary project and a beautiful human adventure between a retinal biologist like Serge Picaud, and myself, a wave physicist for medicine,” declares Tanter, Inserm research director at the Physics for Medicine unit in Paris (ESPCI Paris/PSL Université/Inserm/CNRS).

“The development of a clinical trial of sonogenetic therapy still has many steps to go through to validate its efficacy and safety. If the results are confirmed, this therapy could succeed in restoring patients’ vision in a stable and safe manner,” concludes Picaud, Inserm research director and director of the Vision Institute (Sorbonne Université/Inserm/CNRS).

[1] Outermost layer of the meninges that protect the brain

A “Nano-Robot” Built Entirely from DNA to Explore Cell Processes

Scientists have designed a “nano-robot” made up of three DNA origami structures. © Gaëtan Bellot/Inserm

Constructing a tiny robot from DNA and using it to study cell processes invisible to the naked eye… You would be forgiven for thinking it is science fiction, but it is in fact the subject of serious research by scientists from Inserm, CNRS and Université de Montpellier at the Structural Biology Center in Montpellier[1]. This highly innovative “nano-robot” should enable closer study of the mechanical forces applied at microscopic levels, which are crucial for many biological and pathological processes. It is described in a new study published in Nature Communications.

Our cells are subject to mechanical forces exerted on a microscopic scale, triggering biological signals essential to many cell processes involved in the normal functioning of our body or in the development of diseases.

For example, the feeling of touch is partly conditional on the application of mechanical forces on specific cell receptors (the discovery of which was this year rewarded by the Nobel Prize in Physiology or Medicine).

In addition to touch, these receptors that are sensitive to mechanical forces (known as mechanoreceptors) enable the regulation of other key biological processes such as blood vessel constriction, pain perception, breathing or even the detection of sound waves in the ear, etc.

The dysfunction of this cellular mechanosensitivity is involved in many diseases – for example, cancer: cancer cells migrate within the body by sounding and constantly adapting to the mechanical properties of their microenvironment. Such adaptation is only possible because specific forces are detected by mechanoreceptors that transmit the information to the cell cytoskeleton.

At present, our knowledge of these molecular mechanisms involved in cell mechanosensitivity is still very limited. Several technologies are already available to apply controlled forces and study these mechanisms, but they have a number of limitations. In particular, they are very costly and do not allow us to study several cell receptors at a time, which makes their use very time-consuming if we want to collect a lot of data.

DNA origami structures

In order to propose an alternative, the research team led by Inserm researcher Gaëtan Bellot at the Structural Biology Center (Inserm/CNRS/Université de Montpellier) decided to use the DNA origami method. This enables the self-assembly of 3D nanostructures in a pre-defined form using the DNA molecule as construction material. Over the last ten years, the technique has allowed major advances in the field of nanotechnology.

This enabled the researchers to design a “nano-robot” composed of three DNA origami structures. Of nanometric size, it is therefore compatible with the size of a human cell. It makes it possible for the first time to apply and control a force with a resolution of 1 piconewton, namely one trillionth of a Newton – with 1 Newton corresponding to the force of a finger clicking on a pen. This is the first time that a human-made, self-assembled DNA-based object can apply force with this accuracy.


The team began by coupling the robot with a molecule that recognizes a mechanoreceptor. This made it possible to direct the robot to some of our cells and specifically apply forces to targeted mechanoreceptors localized on the surface of the cells in order to activate them.

Such a tool is very valuable for basic research, as it could be used to better understand the molecular mechanisms involved in cell mechanosensitivity and discover new cell receptors sensitive to mechanical forces. Thanks to the robot, the scientists will also be able to study more precisely at what moment, when applying force, key signaling pathways for many biological and pathological processes are activated at cell level.

“The design of a robot enabling the in vitro and in vivo application of piconewton forces meets a growing demand in the scientific community and represents a major technological advance. However, the biocompatibility of the robot can be considered both an advantage for in vivo applications but may also represent a weakness with sensitivity to enzymes that can degrade DNA. So our next step will be to study how we can modify the surface of the robot so that it is less sensitive to the action of enzymes. We will also try to find other modes of activation of our robot using, for example, a magnetic field,” emphasizes Bellot.


[1] Also contributed to this research: the Institute of Functional Genomics (CNRS/Inserm/Université de Montpellier), the Max Mousseron Biomolecules Institute (CNRS/Université de Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/Université de Bordeaux) and the Physiology and Experimental Medicine: Heart-Muscles laboratory (CNRS/Inserm/Université de Montpellier).

Using Mechanical Tools Improves Our Language Skills


aires cérébrales liées au langage

The brain regions associated with language have increased during periods of technological boom, when the use of tools became more widespread. © Adobe stock


Our ability to understand the syntax of complex sentences is one of the most difficult language skills to acquire. In 2019, research had revealed a correlation between being particularly proficient in tool use and having good syntactic ability. A new study, by researchers from Inserm, CNRS, Université Claude Bernard Lyon 1 and Université Lumière Lyon 2 in collaboration with Karolinska Institutet in Sweden, has now shown that both skills rely on the same neurological resources, which are located in the same brain region. Furthermore, motor training using a tool improves our ability to understand the syntax of complex sentences and – vice-versa – syntactic training improves our proficiency in using tools. These findings could be applied clinically to support the rehabilitation of patients having lost some of their language skills. This study is published in November 2021 in the journal Science.

Language has long been considered a very complex skill, mobilizing specific brain networks. However, in recent years, scientists have revisited this idea.

Research suggests that brain areas, which control certain linguistic functions, such as the processing of word meanings, are also involved in controlling fine motor skills. However, brain imaging had not provided evidence of such links between language and the use of tools. Paleo-neurobiology[1] has also shown that the brain regions associated with language had increased in our ancestors during periods of technological boom, when the use of tools became more widespread.

When considering this data, research teams couldn’t help wondering: what if the use of certain tools, which involves complex movements, relies on the same brain resources as those mobilized in complex linguistic functions such as syntax?


Syntax exercises and use of tongs

In 2019, Inserm researcher Claudio Brozzoli in collaboration with CNRS researcher Alice C. Roy and their team had shown that individuals who are particularly proficient in the use of tools were also generally better at handling the finer points of Swedish syntax.

In order to explore the subject in greater depth, the same team, in collaboration with CNRS researcher Véronique Boulenger[1], developed a series of experiments that relied on brain imaging techniques (functional magnetic resonance imaging or MRI) and behavioral measurements. The participants were asked to complete several tests consisting of motor training using 30 cm-long pliers and syntax exercises in French. This enabled the scientists to identify the brain networks specific to each task, but also common to both tasks.

They discovered for the first time that the handling of the tool and the syntax exercises produced brain activations in common areas, with the same spatial distribution, in a region called the “basal ganglia”.


ganglions de la base

The handling of the tongs and the syntax exercises proposed to the participants produced activations in a region called “basal ganglia”. © Claudio Brozzoli


Cognitive training

Given that these two skill types use the same brain resources, is it possible to train one in order to improve the other? Does motor training with the mechanical tongs improve the understanding of complex phrases? In the second part of their study, the scientists looked at these issues and showed that this is indeed the case.

This time, the participants were asked to perform a syntactic comprehension task before and after 30 minutes of motor training with the pliers (see box for details of the experiment). With this, the researchers demonstrated that motor training with the tool leads to improved performance in syntactic comprehension exercises.

In addition, the findings show that the reverse is also true: training of language faculties, with exercises to understand sentences with complex structure, improved motor performance with the tool.

Motor training and syntax exercises

The motor training involved using the pliers to insert small pegs into holes that matched their shape but with differing orientations.

The syntax exercises which were completed before and after this training consisted of reading sentences with a simple syntax, such as “The scientist who admires the poet writes an article” or with a more complex syntax, such as “The scientist whom the poet admires writes an article.” Then the participants had to decide whether statements such as “The poet admires the scientist” were true or false. Sentences with the French object relative pronoun “que” are more difficult to process and therefore performance was generally poorer.

These experiments show that after motor training, the participants did better with the sentences that were considered to be more difficult. The control groups, which performed the same linguistic task but after motor training using their bare hands or no training at all, did not show such an improvement.

The scientists are now thinking about how to best apply these findings in the clinical setting. “We are currently devising protocols that could be put in place to support the rehabilitation and recovery of language skills of patients with relatively preserved motor faculties, such as young people with developmental language disorders. Beyond these innovative applications, these findings also give us an insight into how language has evolved throughout history. When our ancestors began to develop and use tools, this proficiency profoundly changed the brain and imposed cognitive demands that may have led to the emergence of certain functions such as syntax,” concludes Brozzoli.


[1] A field in which scientists study the evolution of our ancestors’ brain anatomy.

[2] Involved in these findings are the Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1) and the Dynamics of Language laboratory (CNRS/Université Lumière Lyon 2).

Chatbot for addressing COVID-19 vaccine hesitancy

ordinateurResearchers from the CNRS, INSERM, and ENS-PSL show that such an interface is indeed capable of swaying the vaccine-hesitant. © seth schwiet on Unsplash


  • A considerable fraction of the population is reluctant to get vaccinated against COVID-19.
  • French scientists have designed a chatbot that offers personalised responses to questions posed by the curious or hesitant—and have demonstrated its effectiveness.

What if a few minutes of interaction with a chatbot could effectively address vaccine concerns? In an article published in the Journal of Experimental Psychology: Applied (28 October 2021), researchers from the CNRS, INSERM, and ENS-PSL show that such an interface is indeed capable of swaying the vaccine-hesitant.

Vaccine hesitancy is one of the major challenges in containing the COVID-19 pandemic. Previous studies have revealed that mass communication—through short messages relayed by television or radio—is not a very effective means of persuading the hesitant. In contrast, discussing your particular concerns with an expert whom you trust can be more persuasive, but having a face-to-face talk with every vaccine-hesitant individual is impractical.

To overcome this problem, a team of cognitive scientists from the Institut Jean-Nicod (CNRS / ENS-PSL) and the Laboratoire de Neurosciences Cognitives et Computationnelles (INSERM / ENS-PSL) created a chatbot that provides users with answers to 51 common questions about COVID-19 vaccines.1

Chatbots have the advantage of offering quick, personalized Q and A sessions while reaching a large number of people.

The team tested their chatbot with 338 individuals and compared their reactions to those of a control group of 305 participants who only read a brief paragraph that gave information about COVID-19 vaccines. After a few minutes of interaction with the chatbot, the number of participants with positive views of vaccination increased by 37%. People were also more open to getting vaccinated after using the chatbot: declarations of vaccine refusal fell 20%. Such changes in attitude were negligible in the control group.

It remains to be shown whether the effects of chatbot interaction are lasting, and whether they are the same across age groups, and among those most resistant to vaccination.2

Nevertheless, this study has demonstrated that a chatbot can indirectly reach a very large audience: half of the experimental group later tried to persuade others to get vaccinated, with three-quarters of them stating they drew on information provided by the chatbot to do so.

These findings suggest that a chatbot regularly updated to reflect the latest vaccine science could be an effective tool to help reduce vaccine hesitancy.



1The questions were selected on the basis of surveys on reasons for vaccine hesitancy as well as articles about vaccine-related preconceptions. Their answers were prepared from scientific sources and approved by COVID-19 vaccine specialists.

2On average, the group of participants was younger and more educated than the overall population.

Weightlessness: A Challenge for Both the Body and the Brain!

Etude des mouvements

3D motion capture ©Inserm/Guénet, François


With one week to go before astronaut Thomas Pesquet sets out on his space mission Alpha, knowledge about how we adapt to gravity here on Earth is progressing. Researchers from Inserm and Université de Bourgogne within the Cognition, Action and Sensorimotor Plasticity (CAPS) laboratory are interested in how the movements that depend on this omnipresent force are carried out.

For the past 30 years, it was thought that the brain – responsible for motor control – worked to continuously compensate for the effects of gravity. In an initial study in 2016, the researchers had suggested that our brains use gravity to minimize the effort our muscles have to make. Those results were recently confirmed by new experiments conducted in collaboration with New York University on non-human primate models and humans, the findings of which have been published in Science Advances.


Our brain uses the effects of gravity to minimize the physical exertion required.

In order to perform our many activities, the movements of our limbs need to be precise. For a movement to be successful, the brain must generate muscle contractions by anticipating the environmental factors liable to affect that movement. One of the most important of these factors is gravity. The brain develops an internal representation of gravity that it can use to anticipate its effects on our body.


What is the purpose of this anticipation?

Initially, the researchers thought that the brain continuously compensated for the effects of gravity to achieve movements undisturbed by them. Recent studies by researchers from Université de Bourgogne and Inserm at the CAPS laboratory in collaboration with a team from New York University (Dora E. Angelaki, Professor of Neuroscience at the Tandon School of Engineering – New York) challenge this idea. The researchers hypothesized that anticipating the effects of gravity allows us to plan movements that use those effects on our bodies to minimize our muscular exertion.

To confirm this theory, the research team recorded the activations that the brain sends to the muscles. These recordings were made in non-human primates and humans performing horizontal and vertical arm movements.

The information obtained show that the brain sends electrical commands that activate and deactivate the muscles in a very precise way – phenomena that last just a few milliseconds – in order to harness the effects of gravity to accelerate our downward movements and decelerate our upward movements. These findings were observed in both the non-human primates and humans.

This observation supports the hypothesis of profound nervous system adaptation to its environment. 

In the long term, this new knowledge could be put to use in various fields such as movement assistance for people with disabilities or the programming of humanoid robot movements.

Huntington’s Disease: Exploring the Avenue of a Potential Neuroprotective Treatment


Huntington’s disease is a rare and hereditary neurodegenerative disorder. A striatal neuron expresses the causative mutant huntingtin protein (red), which accumulates in the nucleus (blue) to form an aggregate of huntingtin and other proteins, including ubiquitin (yellow). © Frédéric Saudou


Huntington’s disease is a hereditary disorder that causes degeneration of the neurons involved in cognitive, motor and psychiatric functions. While existing treatments address the symptoms and relieve certain aspects of the disease, they cannot alter its course. Researchers from Inserm, Université Grenoble Alpes and Grenoble Alpes University Hospital at the Grenoble Institute of Neuroscience are hoping to remedy this. They are studying a new therapeutic approach in the hope of offering patients the first neuroprotective treatment – one that protects neurons – in the years to come. The therapeutic molecule in question has shown promising results in mice and is currently undergoing preclinical evaluation. Their research has been published in Science Advances.

Huntington’s disease is a rare and hereditary neurodegenerative disorder. It usually begins between the ages of 30 and 50 and manifests with cognitive disorders, psychiatric disorders and uncontrolled movements that worsen over time until death some 20 years later. In France, this condition affects around 18,000 people: 6,000 already have symptoms, whereas around 12,000 carry the mutated gene and will develop symptoms later. The team of Frédéric Saudou, Director of the Grenoble Institute of Neuroscience (Inserm/Université Grenoble Alpes/Grenoble Alpes University Hospital), is working on a new therapeutic approach in an attempt to provide solutions for these patients.

The disease is caused by an abnormality on the gene coding for the protein huntingtin, which interacts with and regulates the activity of at least 400 other proteins involved in various cell functions, including the transport of molecules. This abnormality leads to a reduction in the transport of a key molecule, BDNF, in the brain between the cortex and the striatum. The role of this molecule is to promote the survival of neurons and ensure the connections between them. This reduced transport therefore causes the death of neurons in these brain regions.

“Long before symptoms develop, a reduction in BDNF transport is observed. This molecule is essential for the survival of neurons and for neural connections between the cortex and striatum – two regions involved, among other things, in mood and movement control,” explains Saudou, a professor at Université Grenoble Alpes and Grenoble Alpes University Hospital.

The researcher and his colleagues therefore thought that restoring its circulation would at least afford the brain partial protection from neuron death.


A molecule to restore BDNF transport

In collaboration with Inserm Research Director Sandrine Humbert, Saudou and his team had previously shown that BDNF is transported within vesicles made up of numerous proteins, including huntingtin. In this new study, the researchers identified an enzyme that regulates the transport of these BDNF vesicles by controlling a cell mechanism known as “palmitoylation.” By increasing palmitoylation with the help of a molecule called ML348, they were able to restore the transport of BDNF vesicles.

Several in vitro experiments on human neurons and in vivo experiments on mice have shown that ML384 crosses the blood-brain barrier and restores BDNF traffic from the cortex to the striatum. When administered in a mouse model of the disease, it reversed the symptoms.

Injecting ML348 reduced the motor and psychiatric behavioral disorders, allowing the mice to regain activity close to that of their healthy counterparts,” explains Saudou. What is more, this molecule improves BDNF transport in human neurons derived from induced pluripotent stem cells (iPS cells) from Huntington’s patients, demonstrating that this molecule is potentially capable of having an effect in humans.

Following this proof of concept, the researcher and his team will move on to the preclinical testing phase to evaluate, using cell and animal models, the behavior of the molecule in the body, its safety, and identify effective doses. The ultimate goal is to develop a drug for patients. If these results are confirmed, this molecule could become the first “neuroprotective” treatment for Huntington’s disease, sparing certain neurons from degeneration and perhaps slowing its progression.

A New Method for Unlocking the Mysteries of Life

To better characterize molecular interactions, researchers must also look at molecular chirality. © Valérie Gabelica

Understanding the three-dimensional structure of DNA and RNA and how they interact with other molecules is necessary for the advancement of biomedical research and drug development. A team led by Inserm researcher Valérie Gabelica at the Nucleic acids: natural and artificial regulation laboratory (ARNA, Inserm/CNRS/Université de Bordeaux)[1] has developed an innovative method pairing mass spectrometry with circularly polarized light, enabling better characterization of these different molecular interactions. This new technique is described in a study published in the journal Science.

A technique widely used in physics and biology laboratories, and also in forensic science to analyze chemical and biological samples, mass spectrometry measures the masses of each molecule in a sample, thereby providing information on how they interact and associate with each other.

Inserm researcher Valérie Gabelica and her team at the ARNA laboratory (Inserm/CNRS/Université de Bordeaux)1 are studying how short DNA and RNA sequences fold in three dimensions and interact with other molecules. To do this, they use mass spectrometry, which gives them valuable insights into how DNA and RNA associate structurally with proteins or pharmaceutical molecules, for example.

However, to better characterize these molecular interactions, the scientists must also look at molecular chirality. A molecule is said to be “chiral” when its 3D structure cannot be superimposed onto its mirror image. Due to its helical shape, DNA is therefore a chiral molecule.

Determining the chirality of a molecule is important for understanding its biological interactions with DNA and proteins – the molecules of living organisms.

Given that measuring molecular weight provides no information on chirality, the use of another technique, circularly polarized light[2], is necessary to study the 3D structure of molecules.

In a study published in Science, the researcher and her team describe a novel tool for studying chirality and how DNA and molecules assemble: a “2-in-1” method pairing a mass spectrometer and a laser that produces circularly polarized light.

Therapeutic prospects

The use of such a technique could open up new biomedical research avenues, particularly in neurodegenerative diseases, such as Alzheimer’s.

Indeed, several studies have shown that upstream of the protein aggregation process that forms senile plaques in the brain, the proteins form small complexes known as oligomers, which could be even more toxic. Applying the method developed by the researchers would make it possible to improve our understanding of when these oligomers change their 3D structure, in order to explore the role they play in disease exacerbation and plaque formation.

Another practical application is drug development. For example, if the target of a drug is a chiral protein, it is also important to characterize the chirality of the drug in order to find out more about its potential interactions.

“In the 1960s, thalidomide, a drug taken by many pregnant women to reduce nausea, caused severe birth defects in their babies. In fact, one of the images of this molecule in the mirror was anti-nausea, the other was toxic. A more in-depth study of the molecular structure and chirality would have prevented this,” emphasizes Gabelica.

By pushing back hard on the frontiers of mass spectrometry and facilitating the study of molecule chirality, this research is particularly innovative and opens up very broad prospects in the field of biomedical research.


[1] The IECB research support unit (CNRS/Université de Bordeaux/Inserm) also participated in this work.

[2]Light is a wave. It is described by signals that oscillate in space and time: electric and magnetic fields. These two fields have a direction, the magnetic field is perpendicular to the electric field. When light is circularly polarized, the electric field changes orientation along the beam and describes a spiral. The magnetic field is always perpendicular to the electric field

Music or Speech? The Brain is Divided…

Photo by Thanos Pal on Unsplash

When it comes to recognizing a melody or understanding a spoken sentence, the human brain does not mobilize its hemispheres in an equivalent way. Although the concept is recognized by scientists, there had been no physiological or neural explanation for the phenomenon until now. A team co-led by Inserm researcher Benjamin Morillon at the Institute of Systems Neuroscience (Inserm/Aix-Marseille Université) in collaboration with researchers at Montreal Neurological Institute and Hospital of McGill University has been able to show that, due to different receptivities to the components of sound, the left auditory cortex neurons participate in the recognition of speech, whereas the right auditory cortex neurons participate in that of music. These findings, to be published in the journal Science, suggest that the respective specializations of the brain hemispheres for music and speech enable the nervous system to optimize the processing of sound signals for communication purposes.

Sound is produced from a complex set of air vibrations, which, when reaching the cochlea of the inner ear, are distinguished according to their speed. At any given moment, slow vibrations are being translated into deep sounds and rapid vibrations into high-pitched ones. As a result, sound can be represented according to two dimensions: spectral (frequency) and temporal (time).

These two auditory dimensions are fundamental because it is their simultaneous combination that stimulates the neurons of the auditory cortex. The latter are thought to discriminate sounds that are relevant for individuals, such as those used for communication enabling people to talk to and understand each other.

In humans, speech and music constitute the main uses of sound and the most complex on the cognitive level. The left hemisphere is primarily implicated in the recognition of speech, whereas the right hemisphere is primarily implicated in that of music. However, until now little was known about the physiological and neural reasons for this asymmetry.

A team co-led by Inserm researcher Benjamin Morillon at the Institute of Systems Neuroscience (Inserm/Aix-Marseille Université) in collaboration with researchers at Montreal Neurological Institute and Hospital of McGill University used an innovative approach to understand how speech and music are decoded within each of the human brain hemispheres.

The researchers recorded 10 sentences sung by a soprano to 10 new melodies composed especially for the experiment. These 100 recordings, in which melody and speech are dissociated, were then distorted by decreasing the amount of information present in each dimension of the sound. Forty-nine participants were asked to listen to pairs of these distorted recordings, and to determine whether they were identical in terms of speech content and melody. The experiment was conducted in French and English speakers to see whether the results were reproducible in different languages.

A demonstration of the audio test proposed to the participants is available here: temporal modulations/

The research team found that for both languages, when the temporal information was distorted, participants had trouble distinguishing the speech content, but not the melody. Conversely, when the spectral information was distorted, they had trouble distinguishing the melody, but not the speech.

Functional magnetic resonance imaging (fMRI) of the participants’ neural activity showed that in the left auditory cortex the activity varied according to the sentence presented but remained relatively stable from one melody to another, whereas in the right auditory cortex the activity varied according to the melody presented but remained relatively stable from one sentence to another.

What is more, they found that degradation of the temporal information affected only the neural activity in the left auditory cortex, whereas degradation of the spectral information only affected neural activity in the right auditory cortex. Finally, the participants’ performance in the recognition task could be predicted simply by observing the neural activity of these two areas.

Original a capella extract (bottom left) and its spectrogram (above, in blue) broken down according to the amount of spectral and temporal information (center). The right and left cerebral auditory cortexes (right) decode melody and speech respectively.

“These findings indicate that in each brain hemisphere, neural activity depends on the type of sound information, specifies Morillon. While temporal information is secondary for recognizing a melody, it is essential for the correct recognition of speech. Conversely, while spectral information is secondary for recognizing speech, it is essential for recognizing a melody. “

The neurons in the left auditory cortex are therefore considered to be primarily receptive to speech thanks to their superior temporal information processing capacity, whereas those in the right auditory cortex are considered to be receptive to music thanks to their superior spectral information processing capacity. “Hemispheric specialization could be the nervous system’s way of optimizing the respective processing of the two communication sound signals that are speech and music,” concludes Morillon.

This research was supported by a Banting fellowship to Philippe Albouy, grants from the Canadian Institutes of Health Research and the Canadian Institute for Advanced Research to Robert J. Zatorre, ANR-16-CONV-0002 (ILCB) and ANR-11-LABX-0036 (BLRI) funding and the Excellence Initiative of Aix-Marseille Université (A*MIDEX).”