Choc Santé (Health Shock): Inserm is releasing a collection of books for the general public.

In partnership with Muscadier publishing house, Inserm (French National Health and Medical Research Institute) is creating a series of books to inform the public about health matters. These books shall provide an overview of the Institutes’s latest research results in 128 pages. They are intended for both patients and their families who act as caregivers.

The Collection

Everybody wants to be healthy. Diet, physical activity and general lifestyle have become important concerns for most of us. In terms of treatment and prevention, scientific advances in recent decades have opened up unprecedented opportunities. However, we do not always know where to find the most relevant information. As such, we often hear or read everything and anything regarding this specific area.

Who should we believe? How do we find out?

The Choc Santé collection aims give a much wider audience access to knowledge gathered by Inserm, who has carried out public research in the health sector for over 50 years. As well as the latest medical advances, the reader will find practical advice that will enable them to improve their health and the health of those close to them.

The first two Choc titles: Alzheimer’s Disease and Depression

Medical research is making great strides and substantial progress in many fields, which often gives cause for hope. An overview of the latest information concerning Alzheimer’s disease and depression, both works will allow everyone to better understand the disease and improve the lives of patients and relatives.PhotoCP web

Alzheimer : fatalité ou espoir ? (Alzheimer’s Disease: Inevitable or Hopeful?)

The Book

Almost everyone knows somebody who has been affected by Alzheimer’s disease. Yet, most of us know little about this condition, which often has a dramatic impact on both the patient and those around them. What are the causes? What are the symptoms? How to detect and monitor it? When is diagnosis possible and desirable? What treatments are available? How does it progress? Is it inevitable or can we influence its onset and progression in some way?


Francis Eustache is the Director of Studies at the École pratique des hautes études (EPHE) and Director of Inserm Research Unit 1077, “Cognitive Neuropsychology and Functional Neuroanatomy of Human Memory” (Inserm-EPHE-University of Caen Lower Normandy) He is one of the foremost international specialists on memory-related issues. Gaëlle Chételat, Béatrice Desgranges and Vincent de La Sayette are also members of Research Unit 1077.

Dépression : s’enfermer ou s’en sortir ? (Depression: Shackled or Surmountable?)

The Book

“To have depression”, “to be depressed”, etc., everyone has used these terms to describe a malaise or a passing mood. However, depression is a real illness that affects millions of people in France. This condition raises many questions as it affects different people in different ways. What are the symptoms? What are the causes? Can it be treated? Are current treatments effective? Are they dangerous? What support can we give to a person with depression?


Antoine Pelissolo is a psychiatrist and Department Head at CHU Henri Mondor Créteil, Professor of Medicine at Paris-East University, and President of the French Association of Anxiety Disorders and Depression (AFTAD). He conducts clinical and therapeutic research on these diseases in the Inserm unit at the Mondor Institute of Biomedical Research and in the FondaMental foundation.

Towards a new weapon against muscular dystrophy

Research efforts associating scientists from the CNRS, UVSQ and INSERM within the Laboratoire END-ICAP[1], working in collaboration with a team from the University of Bern, has demonstrated the therapeutic potential of a new class of synthetic oligonucleotides[2] in the treatment of Duchenne muscular dystrophy (DMD) using RNA “surgery”. Tested in the mouse, this new generation of molecules proved to be clinically superior to those currently under evaluation in DMD patients, notably for restoring cardio-respiratory and central nervous system function. These findings were published on 2 February 2015 in Nature Medicine.

Etude de la myopathie de Duchenne

Study of Duchenne Muscular Dystrophy-  Necrotic lesions (cellular death) of muscular fibers made up of myofribils. Gomori trichrome stain. ©Inserm/Fardeau, Michel

Neuromuscular diseases include several hundred conditions, mainly of genetic origin, which are defined by a defect in muscle control or the destruction of muscle tissue. Taken together, they affect tens of thousands of people in France, and represent a major public health challenge. The most emblematic of these conditions, Duchenne Muscular Dystrophy (DMD) is caused by mutations that affect the gene coding for dystrophin, a protein essential for the correct functioning of muscle cells. This particularly severe and disabling disease does not yet benefit from any satisfactory treatment.

RNA “surgery” is an approach that has been developed in order to correct certain genetic abnormalities. This therapy is based on using small sequences of antisense oligonucleotides (AON)[3] that can bind to — and specifically act on — messenger RNA, and allow the synthesis of a missing protein. Several studies are underway to synthesize different types of AONs designed to act on dystrophin production. Despite the encouraging results of some clinical trials, existing AONs have limitations: their level of toxicity is sometimes high and they cannot act at the cardiac level or cross the blood-brain barrier. Designing a therapy that would be effective simultaneously for all skeletal muscles, the heart and the central nervous system, remains a challenge.

The authors of this work have developed new nucleotides for AON synthesis: tricyclo-DNA (tcDNA). These AON-tcDNA, synthetic analogs of DNA, hybridize with target RNA and cause the excision of a fragment of RNA[4]. By acting on that part of the gene that carries an error, they allow the synthesis of a truncated — but stable and functional — dystrophin. The monitoring of DMD mice treated with these AON-tcDNA has shown that these analogs perform better than their previous equivalents. Administered intravenously, the AON-tcDNA are efficiently distributed throughout the skeletal muscle, and also reach the cardiac tissue and central nervous system, which was not the case for their predecessors. In addition, the restoration of dystrophin production is more effective than with previous AONs. After a twelve-week treatment, the mice displayed highly significant improvements, not only in muscle function but also in cardio-respiratory function, which are the principal targets in patients suffering from this neuromuscular disease.

The scientists also demonstrated a correction of emotional responses, which are naturally exacerbated in DMD subjects and may cause learning disabilities and cognitive defects. This part of the study, performed in collaboration with a team from the Institut des Neurosciences Paris Saclay (CNRS/Université Paris-Sud), showed that dystrophin is crucial to the proper functioning of certain neurons and that the behavioral disorders observed in the context of a dystrophin deficit were at least partially reversible in adult mice with DMD.

As well as these promising results, AON-tcDNA are characterized by a lengthy residence time within tissues, which in the future will allow treatments to be administered at longer intervals. Another advantage is that they are not degraded but gradually excreted by the body, thus making the treatment reversible and limiting its toxicity. The toxicological analyses required are still ongoing but their initial results suggest that these new AONs are well tolerated at high doses in mice.

The mechanisms responsible for the efficacy of these third-generation AONs are still poorly understood but several of their properties may be involved, including notably their strong affinity for RNA and their ability to form “nanoparticle” aggregates in a spontaneous manner.

The chemistry of tcDNA thus opens numerous perspectives for their application in various genetic diseases. Above all, this is a new step towards a systemic drug therapy[5] for Duchenne muscular dystrophy.

Clinical trials in humans are scheduled within the next 18 to 24 months, in collaboration with the company, Synthena.

This work was carried out as part of a large international collaborative project (ICE – International Collaborative Effort for DMD) at the initiative of the Monaco Association Against Muscular Dystrophy (AMM) and the Duchenne Parent Project France (DPP-F), and received partial support from the HandiMedEx Chair of Excellence under the French Investments for the Future (Investissements d’Avenir) program.

[1] Laboratoire END-ICAP: Handicap neuromusculaire: physiopathologie, biotechnologies et pharmacologies appliquées (UVSQ/Inserm) forms an integral part of the International Associated Laboratory for “Biotherapies Applied to Neuromuscular Disabilities” (LIA BAHN – UVSQ/CSM).

[2] Oligonucleotides are short segments of nucleic acids (RNA or DNA).

[3] These sequences are called antisense because they complement messenger RNA. The synthetic strand will thus have a sequence that is the reverse of that of the RNA strand.

[4]  After the transcription of DNA into RNA, the latter undergo a number of changes, including splicing, during which non-coding fragments will be excluded in order to produce mature RNA used for translation into proteins.

[5] Administered systemically.

Osteoporosis : balancing bone formation and degradation

Most existing treatments for pathological bone loss inhibit osteoclasts (bone-destroying cells) to limit bone degradation. However, by doing this, they also prevent bone formation since it is stimulated by the presence of these very same osteoclast cells. Researchers from the CNRS, Inserm and the Université de Montpellier and Université Jean Monnet – Saint-Étienne[1] have developed a new approach for preventing the destructive activity of osteoclasts without affecting their viability. This involves disrupting their anchorage to the bone, which has been found to be possible using a small chemical compound called C21. This innovative treatment can protect mice from bone loss associated with osteolytic diseases[2] such as post-menopausal osteoporosis, rheumatoid arthritis and bone metastasis, without affecting bone formation. This research was published on 3 February 2015 in the journal Nature Communications.Culture d'ostéoclastes

© Inserm/Boivin, Georges

Bone is a highly dynamic tissue that is constantly in the process of being simultaneously destroyed and reconstructed. This dynamism is ensured by good coordination between the cells that destroy the “old” bone (osteoclasts) and those that reconstruct it (osteoblasts). In some diseases, bone degradation by osteoclasts exceeds bone formation by osteoblasts. As such, the challenge faced by researchers is to control osteoclast activity to avoid too high a rate of bone degradation leading to osteoporosis. However, osteoblast activity is stimulated by the presence of osteoclasts and, therefore, it is essential to find treatments for osteoporosis that reduce the activity of osteoclasts without affecting their viability.

To destroy bone, osteoclasts use specific cell structures called podosomes, which are organized into rings by the actin cytoskeleton. Podosomes act like “snap fasteners” between the bone and the osteoclast by forming a kind of “suction cup” in which the bone is degraded. The researchers have shown that the exchange factor3 Dock5 activates a small enzyme called GTPase Rac, to organize the actin cytoskeleton and allow the formation of the ring of podosomes. Using different mouse models of pathological bone loss (post-menopause osteoporosis, rheumatoid arthritis and bone metastases), the scientists have discovered that administering a synthetic compound called C21, which inhibits Dock5, prevents osteoclast activity by blocking the “suction cup” effect that otherwise enables them to destroy the bone. Because the osteoclasts are still present, bone formation can still take place during treatment.

In mice, these results validate the pharmacological inhibition of Dock5 as a new therapeutic pathway. The researchers are now seeking to develop more compounds that inhibit Dock5, other than C21, in order to continue fighting osteolytic diseases while preserving bone formation.
[1] From the Centre de recherche de biochimie macromoléculaire (CRBM) [Centre for Biochemical and Macromolecular Research] (CNRS/Université de Montpellier), Laboratoire d’enzymologie et biochimie structurale (LEBS) [Laboratory of Enzymology and Structural Biochemistry] (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM) [Montpellier Cancer Research Institute] (Inserm/ Université de Montpellier) and Laboratoire de biologie intégrative du tissu osseux [Laboratory of integrative biology of bone tissue] (Inserm/Université Jean Monnet – Saint-Étienne).

[2] Diseases related to the degradation of bone tissue.

Road safety: presentation of the French government’s next action plan

Bernard Cazeneuve, French Minister of the Interior, presented a plan of action to address all causes of lack of road safety on Monday 26 January 2015. Comprising 26 measures, the plan is aimed at sensitising, alerting and educating road users, combating serious breaches of road safety, and making France’s infrastructure safer.[1]

In 2014, according to the French National Interministerial Observatory for Road Safety (ONISR), 3,388 people lost their lives on France’s roads, a figure which represents a 3.7% increase, or 120 more deaths than in 2013.

These measures include, in particular, a reduction in the legal blood alcohol level from 0.5 g/l (grams per litre of blood) to 0.2 g/l for young drivers, together with a reduction in the maximum authorised speed from 90 to 80 km/h on some roads for two years, in order to observe the effect on the number of accidents.

There are also plans for a ban on the use of all systems requiring earpieces, earbuds or headsets that could restrict the attention and hearing of drivers

According to the collective expert report “Téléphone et Sécurité Routière” (Telephones and Road Safety), telephone use while driving trebles the number of accidents.

In 2011, Inserm confirmed the hazard associated with using a telephone while driving in the collective expert report “Téléphone et Sécurité Routière.” This report highlights the growing use of “distractors,” such as embedded systems and touch screens, which when used while driving, although banned since 2008, disturb the driver’s concentration, seriously threatening his/her safety and that of other road users.

[1] Mr Bernard Cazeneuve’s speech presenting the action plan on road safety can be consulted on the Ministry of Interior website: