a semester of breakthroughs...2 icm a semester of breakthroughs - n 1 2017 icm a semester of...

ICM A SEMESTER OF BREAKTHROUGHS - N°1 2017 1

N°1 - JULY 2017

B R A I N & S P I N E I N S T I T U T E

SEARCH, FIND, CURE, FOR YOU & WITH YOU.

ON THE CLINICAL ENDFOCAL EPILEPSY

New treatment for seizures

ON THE STARTUP ENDPARKINSON’S DISEASE

Video games for patient rehabilitation

PARKINSON’S DISEASEANTIBIOTICS

BREAKTHROUGHS

P.9

P.13

P.14

A SEMESTER OF

AGAINST

ICM A SEMESTER OF BREAKTHROUGHS - N°1 2017 32 ICM A SEMESTER OF BREAKTHROUGHS - N°1 2017

SUM M A RY

A word f rom our ch ie f execut i ve p.3

A g l oba l cha l l enge p.4

ON THE RESEARCH END p.6

O Behav i o r : when dec i s ions a re b iased p.6

O Al zhe i mer ’s d i sease : a de le te r ious e f fec t o f the immune sys tem ? p.6

O Fra g i l e x syndrome : so lv ing the mechan i sm p.7

O Behav i o r : dec i s ion -mak ing , a contag ious mechan i sm p.8

O Ant i b i o t i c s aga ins t pa rk inson ’s d i sease? p.9

O M ul t i p l e sc le ros i s : toward regenera t ion p.9

ON THE CLINICAL END p.10

O De fe c t i n b ra in deve lopment : d i scovery o f a gene

i nvo l ved i n the p rocess p.10

O Pa rk i nson ’s : vo lun ta ry eye movement , a new ind ica to r

fo r postu ra l cont ro l ? p.11

O Al zhe i mer ’s d i sease : p rogress i n genet i c counse l i ng p.12

O A b i o l og ica l te s t to de tec t c reu tz fe ld t - j akob d i sease p.13

O Foca l ep i l epsy : new t rea tment fo r se i zu res p.13

ON THE STARTUP END p.14

O Pa rk i nson ’s d i sease : v ideo games fo r pat i en t rehab i l i t a t ion p.14

O A l i v i ng l ab p ro to type fo r i nc reased hosp i ta l p r i vacy p.15

One ou t o f eve ry e igh t i nd iv idua l s w i l l be a f fec ted by b ra in o r sp ina l co rd i l l ness th roughout the i r l i f e . We can h igh l igh t d i scove r i e s , ye t we have no t found a cu re . Ma jo r p rogress has been made i n neu ro logy, ye t the re i s so much more l e f t to exp lo re i n the comp lex un ive r se o f the ne rvous sys tem to go fu r the r than pa l l i a t i ve med ic ine , towards cu ra t i ve and p revent i ve med ic ine .So many cha l l enges l i e ahead fo r re sea rche r s .

The f i r s t cha l l enge i s unders tand ing the ne rvous sys tem , bo th i n i t s no rma l s ta te and patho log ica l s t a te . The b ra in and sp ina l co rd a re ex t reme ly comp lex , wh ich i s why i t i s so impor tan t tha t we deve lop exce l l en t f undamenta l re sea rch capab i l i t i e s to unders tand the deve lopment , ag ing , f unc t ions and p l a s t i c i t y o f the ne rvous sys tem and iden t i f y under l y i ng mechan i sms o f ou r behav io r. The second cha l l enge i s ga in ing a deeper unders tand ing o f ne rvous sys tem i l l nesses to p reven t them , mean ing deve lop new s t ra teg ies fo r ea r l y d i agnos i s and t rea tment , and to cu re them , mean ing deve lop i nnovat i ve the rapy and p rec i s ion med ic ine , and s low d i sease p rogress ion .

Our i n s t i t u te i s a un ique 360 ° mode l where pa t i en t s , do c to r s a n d resea rche r s work hand i n h a n d to deve lop fu tu re t rea tmen ts .Trea t i ng b ra in d i seases i s a ma jo r i s sue , e spec i a l l y a s ou r po pu la t io n ages , and soc ie ty a s a w h o le i s faced w i th the cha l l enge o f “a g in g we l l ” . The ICM has a key ro l e to p l ay so tha t each and eve ry o n e o f u s has the oppor tun i ty to a ge i n the best poss ib l e cond i t i o n s , w i th ou r own i ndependence . Th e re i s so much l e f t to exp lo re .

I am p roud to p resen t th i s n ew pub l i ca t ion tha t b r i ngs to ge th e r the ma jo r b reakth roughs o f these past s i x months , t h e re su l t o f yea r s and yea r s o f wo rk . “A Semeste r o f B reakth rough s” w i l l open the doors , tw ice a ye a r i n Ju l y and December, to th e wo rk done by ou r re sea rche r s a n d c l i n i c i ans a t the I n s t i t u te .

Be fo re you embark on a j o u rn ey towards ou r neu rosc i ence ach ievements , I wou ld l i ke to thank the women and m e n th a t he lp us ca r ry th i s g rea t f l a g o f hope , hope tha t we can p reve n t , cu re , and hope fu l l y one day repa i r, mak ing i t poss ib l e to t re a t no t on ly the consequence s , bu t a l so the causes o f ne rvo u s sys te m and sp ina l co rd i l l nesses .

A WORD FROM OUR P RES I DENT

Pr ALEXIS BRICEChief executive


A GLOBAL CHALLENGENEARLY ONE BILLION INDIVIDUALS WORLDWIDE ARE AFFECTED BY NEUROLOGICAL OR PSYCHIATRIC

ILLNESS, AND 80% OF THESE INDIVIDUALS DO NOT BENEFIT FROM APPROPRIATE OR ADEQUATE

TREATMENT. THE CHALLENGE IS HUGE. FOR YEARS, THE INDUSTRY HAS FACED INCREASING FAILURE

RATES IN INNOVATIVE DRUG DEVELOPMENT: 15% OF CANDIDATE DRUGS THAT UNDERGO CLINICAL TESTING

ARE PUT ON THE MARKET, YET THIS FIGURE DROPS TO 7% FOR THE NERVOUS SYSTEM. ADDITIONALLY,

IN THIS EXTREMELY COMPLEX FIELD OVER 12 YEARS ARE NEEDED FOR A DRUG TO BE READY VERSUS,

FOR EXAMPLE, 6.5 YEARS IN THE FIELD OF CARDIOVASCULAR ILLNESS.

THE ICM: A HIGH-LEVEL INSTITUTE FACED WITH EVEN HIGHER STAKES

The ICM’s defining strength is its ability to take into account the whole healthcare process

rather than drugs alone. This approach brings together research, platform and expert support, startup technology and national and international network involvement.

Moreover, success - in particular that of the Center for Clinical Investigation - was obtained through the creation of a collaborative environment between researchers, doctors and patients. In-dustry partnerships between the public and private sector at the ICM helped ac-celerate and turn discoveries into prac-tical treatment solutions for clinical use,

while lowering academic constraints often found in research. The Nervous System Diseases department opens its doors to 100,000 patients every year, who have access to the latest treatment breakthroughs and are active partici-pants in research.

Positioned at the crossroads of vari-ous fields, the ICM asserts a global approach to illness, and is lowering the barriers separating pharmacy, technology and humanities to design integrated healthcare that starts with prevention, leading up to management of disabilities, using technology as a dedicated instrument. This strategy is implemented with the development of a

startup accelerator, currently hosting 16 businesses, the new living lab dedicated to tech solutions, and the neuroinfor-matics project that aims at implement-ing instruments to encourage more predictive and quantitative medicine when it comes to diagnosis, prognosis and therapy.Finally, the creation of a hospital liv-ing lab helps accelerate development of shared early-stage projects with “medtech” companies as well as busi-ness focused on telemedical services. One of the main goals is to increase the number of French startups in the field by dedicating the necessary resources to designing functional prototypes ap-proved for patient use.

I n E u r o p e , 1 i n 8 i n d i v i d u a l s i s a f f e c t e d b y n e rv o u s s y s t e m i l l n e s s

There are several reasons. Prior to finding, you first need to understand. As understand-

ing how our brain functions is crucial, several teams of ICM researchers are working together, pursuing this objective. Then, the major neuro-degenerative diseases share a late appearance of clinical symptoms. For example, the first signs of Parkinson’s disease appear when over 80% of do-paminergic neurons in the substantia nigra have already been destroyed. In the same manner, the brain can be flooded with amyloid plaques without a patient showing any clinical symp-toms of Alzheimer’s yet. Treatment is administered late in the disease, so

its efficacy is limited due to irrevers-ible damage already experienced by the brain. One of the most promising approaches to reach very early detec-tion - at the infraclinical stage - of the disease consists in multimodal bio-marker research on individuals with a high risk of developing the disease. These high-risk individuals are those related to patients with a genetic form of the disease.A second reason lies in the fact that the deign itself of candidate drugs to treat nervous system diseases is com-plicated by the “Great Wall of China” that is the blood-brain barrier, which prevents drugs from passing through. The chemical and protein engineer-

ing required to ensure that a specific therapeutic molecule reaches the ap-propriate target cell is colossal.The third major obstacle in develop-ing drugs that work is the relevance of new targets. Action directed against a certain cellular target can have completely antagonistic effects from one area of the brain to another, increasing the risk of side effects.Finally, lack of knowledge surround-ing disease physiopathology and the inexistence of satisfactory preclinical modelling leads to dramatic failures in drug development.

WHY IS IT TAKING SO LONG TO DEVELOP TREATMENT FOR NERVOUS SYSTEM DISEASES?


Our preferences determine our actions: this may seem obvious,

but the opposite isn’t as simple to grasp. However, it appears that

in certain situations, our past actions influence our current preferences

and judgements.

This transformation of subjective values through our actions can be found in

many different situation both in everyday life and in a laboratory setting. For

example, when students who are against the death penalty are asked to write an

essay in favor of it, researchers found that simply writing about it impacts their

judgement. When an individual acts in a way that opposes their values due to

specific circumstances, they will experience a state of cognitive dissonance, a

state pf psychological strain that they will then attempt to reduce.

Mariam Chammat, Lionel Naccache and their colleagues found that this renowned

psychological phenomenon is closely linked to episodic memory by which we re-

member past experiences and their context (date, location, emotional state). Our

subjective preferences are altered by our past choices only when we remember

them. The discovery of this novel ability as well as the underlying cerebral mecha-

nism shed a new light on cognitive dissonance.

Based on their discovery, the authors put forward an explanation for cognitive

dissonance based on the regulation of subjective coherence in conscious think-

ing: how to agree, today, with what we were in the past and what we remember.

ON THE RESEARCH END

FRAGILE X SYNDROME:

SOLVING THE MECHANISM

The team led by Bassem Hassan at the ICM

collaborated with the VIB at KU Leuven

and a Norwegian team to shed new light on

the neural process at work in Fragile X Syndrome.

This genetic disease affects men twice more

than women due to a genetic mutation affecting

chromosome X and leads to moderate to severe

intellectual disabilities, attention deficit and social

anxiety.

20% of neurons are inhibitory in a healthy brain, mean-

ing that they restrict interneuronal communication

to ensure that information exchanged is precise and

targets specific areas of the brain depending on what

is perceived by the individual or animal.

Using a Drosophilia model, researchers found that

Fragile X Syndrome alters interneuronal communi-

cation. Lack of inhibitory characteristics in certain

neurons leads to background signals during informa-

tion processing that interfere with sensory analysis,

information assimilation, and fly behavior.

A similar inhibitory defect may affect patients with

Fragile X Syndrome. This may lead to hyperexcitability

of certain neural circuits, which would help explain

symptoms such as hypersensitivity, hyperarousal

and epilepsy but may also lead to poor information

processing with an impact on patient behavior. Fragile

X Syndrome and autism as well as Rett Syndrome

have shared characteristics, suggesting that inhibitory

deficit may be a general mechanism in intellectual

deficiency.

BEHAVIOR

WHAT IF OUR PAST ACTIONS INFLUENCED OUR CURRENT VALUE SYSTEM?

“ Our research suggests a potentially

detrimental role played by compromise

(social, political, professional, affective,

moral…), when we accept to act in a way

that is contrary to our values. Although we

may wrongly believe that these acts will

not affect our value system, they can in

fact transform it, with varying degrees of

depth. ” LIONEL NACCACHE (APHP, UPMC)

“ These results suggest that a treatment that

would increase neural inhibition could re-

duce anxiety and epilepsy in certain patients.

The next step is testing inhibition-boosting

drugs that are already approved for patient

use such as benzodiazepines and barbitu-

rates in experimental models followed by

clinical trials. Another opportunity would be

to use sensory testing, such as smell, sound

or color discrimination, to diagnose Fragile

X Syndrome.” BASSEM HASSAN (INSERM)

Cognitive dissonance resolution depends on episodic

memory. Mariam Chammat, Imen El Karoui, Sébastien Allali,

Joshua Hagège, Katia Lehongre, Dominique Hasboun, Michel

Baulac, Stéphane Epelbaum, Agnès Michon, Bruno Dubois,

Vincent Navarro, Moti Salti, Lionel Naccache, Scientific

Report, 23 Janvier 2017.

Reduced Lateral Inhibition Impairs Olfactory Computations

and Behaviors in a Drosophila Model of Fragile X Syndrome.

Franco LM, Okray Z, Linneweber GA, Hassan BA, Yaksi E. Curr

Biol. 2017 Mar 23

ALZHEIMER’S DISEASE A DELETERIOUS EFFECT OF THE IMMUNE SYSTEM?

The immune system plays a very controversial role in Alzheimer’s disease. Does it protect neurons by getting rid of toxic

waste or, on the contrary, does it accelerate disease progression by destroying neurons?

As part of a collaborative project between the Jean-Pierre Aubert Research Center (Inserm UMR-S 1172/Université de Lille),

the ICM and the St Antoine Research Center, scientists studied the activation of the immune system in a mouse model of Tauopathy,

mimicking the degeneration observed in Alzheimer’s disease. Tau proteins are essential in neuron function but their aggregation leads

to dysfunction followed by neural death. They are responsible for one of the two types of lesions found in Alzheimer’s disease, neurofi-

brillary degeneration.

Researchers found that pathogenic T-cells infiltrate the brain, with detrimental consequences on cognitive function. This infiltration of

T-cells can also be found in patients with genetic tauopathy. To understand the role played by T-cells in the disease, they eliminated

the T-cells in mice, leading to improved memory, thereby highlighting the deleterious effects of these cells on cognitive functions.

These T-cells are attracted into the brain by chemokines, inflammatory molecules, that may be a potential therapeutic target.

“ These discoveries are an example of the great progress we’ve made in understanding the underlying mechanisms of Alzheimer’s

disease as well as other neurodegenerative diseases, especially when it comes to the role played by T-cells. We now hope to im-

prove the identification of the type of T-cells involved, understand how they function and when to intervene.”

CÉCILE DELARASSE (UPMC)

Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of Tauopathy. Laurent et al. Brain 2016.


ON THE RESEARCH END

How do we make decisions in everyday life: is it part of

our genetic personality, or a process that comes from

our education and social interactions? Do our neigh-

bor’s decisions impact our own? To answer these questions

and more, Jean Daunizeau and Marie Devaine studied three

characteristics that guide most of our decision-making: cau-

tion, patience and effort or, depending on the point of view,

risk-taking, impatience and laziness. To carry out this study,

they combined mathematics and cognitive psychology.

Researchers recruited participants and had them take decision-

making tests. At first, they had to make choices that involved

varying degrees of patience, effort and caution, for example

choosing between 2 euros now or 10 euros in several days,

pressing a soft handle for low earnings or very hard handle for

a higher amount, or a raffle with a high probability of winning

a small sum or low probability of higher earnings… Participants

were then asked to predict choices made by a fictional char-

acter created with an algorithm that would be more cautious,

lazier, and more patient than the participant, or the opposite.

Every participant spontaneously imagined that the character

would make the same choices as themselves, whatever their

behavior. However, after an adjustment period and several

mistakes, participants became increasingly better at predicting

the algorithm’s answers. Finally, researchers gave participants

a third series of tests and noticed that the choices made by

participants began to resemble those made by the fictional

character.

In a relatively unconscious manner, the participants aligned

their attitudes with the fictional character’s attitude. They were

not aware that the nature of their choice changed, and that

they became more patient or more cautious, for example. This

phenomenon is called social contagion bias.

BEHAVIOR

“ A better understanding of how others influ-

ence decision-making could have implications

in the medical world. We’ve observed high lev-

els of imitation in healthy individuals, and hope

to see whether or not this is true for patients

with psychiatric illnesses that affect social re-

lationships such as autism or schizophrenia. If

we do notice a difference, absence of imitation

may become a component in diagnosis. This

would make it important at a clinical level.”

JEAN DAUNIZEAU (INSERM)

Learning about and from others’ prudence, impatience or lazi-

ness: The computational bases of attitude alignment. Devaine M,

Daunizeau J. PLoS Comput Biol. 2017 Mar 30;13(3):e1005422.

MULTIPLE SCLEROSIS

TOWARD REGENERATION

Why does multiple sclerosis progress more rapidly in some patients than in others? Why do some patients

with multiple sclerosis succeed in repairing demyelination damage over the course of the disease and oth-

ers not?

Multiple sclerosis (MS) is an inflammatory disease of the nervous central system leading to a progressive destruction of

the myelin sheath surrounding axons, essential for their protection and for the transmission of the nerve impulse. Efficient

myelin repair is a key factor in fighting against disease progression. Understanding why and how the illness progresses

more or less rapidly in certain patients is essential.

ICM researchers hypothesized that T-cells, key players in inflammation and myelin destruction, may play a part in remyeli-

nation success or failure.

Using a new experimental model, they highlighted that T-cell activity was enacted through an interaction between mac-

rophages and microglial cells that coordinate repair. In the case of patients with strong remyelination capacities, T-cells

send the appropriate signals to activate repair, leading to cell recruitment and differentiation into myelin-repairing cells.

In the case of patients with low remyelination capacities, T-cells do not enable appropriate microglial activation, thereby

affecting the entire chain of repair.

“ The study of T-cells in patients with strong remyelination capacities is a promising approach that may be helpful in

developing novel strategies for myelin regeneration. This systematic study could help both for diagnosis and treat-

ment in order to develop precise medical care, tailored to each patient, on the long run.” VIOLETTA ZUJOVIC (INSERM),

ISABELLE REBEIX (INSERM) AND BERTRAND FONTAINE (AP-HP, UPMC).

Adaptive human immunity drives remyelination in a mouse model of demyelination. El Behi M, Sanson C, Bachelin C, Guillot-Noël L, Fransson J, Stankoff B, Maillart

E, Sarrazin N, Guillemot V, Abdi H, Cournu-Rebeix I, Fontaine B, Zujovic V. Brain. 2017 Feb 22.

PARKINSON’S

ANTIBIOTICS AGAINST PARKINSON’S DISEASE?

What if an antibiotic that has been used for more than half a century could cure Parkinson’s disease? This is

the hope raised by a study carried out by two researchers from the Brain & Spine Institute, Rita Raisman-

Vozari and Julia Sepulveda-Diaz, in collaboration with a team from Argentina and two teams from Brazil.

Their results show that when used in low doses, an antibiotic called doxycycline can reduce the toxicity of a protein,

α-synuclein, that accumulates in the brain and is involved in the progression of Parkinson’s disease. Through a multidis-

ciplinary approach combining biophysics, biochemistry and neurobiology, the researchers described how doxycycline

would operate, and in particular how it neutralises the toxic forms of α-synuclein.

In an experimental model of Parkinson’s disease, the same teams had previously demonstrated the protective action of

doxycycline on dopaminergic neurons, whose loss is responsible for the disease’s motor disorders. They had also ob-

served its anti-inflammatory action in the brain.

“ This antibiotic is very well tolerated in humans. It is used for example for the treatment of acne, and has the advan-

tage of perfectly penetrating into the brain. These very encouraging results make doxycycline an ideal candidate for

the treatment of Parkinson’s disease and would make it possible to consider starting clinical trials in humans in the

near future.” RITA RAISMAN-VOZARI (CNRS)

Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species. González-Lizárraga

F, Socías SB, Ávila CL, Torres-Bugeau CM, Barbosa LR, Binolfi A, Sepúlveda-Díaz JE, Del-Bel E, Fernandez CO, Papy-Garcia D, Itri R, Raisman-Vozari R, Chehín RN.

Scientific Reports 2017 Feb 3. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model. Lazzarini M, Martin S, Mitkovski M, Vozari RR,

Stühmer W, Del-Bel E. Glia 2013 Jul 6

DECISION-MAKING, A CONTAGIOUS MECHANISM


ON THE CLINICAL END

The two cerebral hemispheres are linked together

and communicate through the corpus callosum,

a kind of bridge that enables information to pass

and participates in the memory and learning processes

in particular. Some people may be born without a corpus

callosum; this is called agenesis of the corpus callosum

and affects one in every 4,000 newborns. This is the most

frequent viable cerebral anomaly.

This cerebral development disorder may be associated with

intellectual disability with varying degrees of severity, or

manifest almost no symptoms. The detection of this malfor-

mation is most often performed during the prenatal period

(ultrasound during the 2nd trimester of pregnancy). The

real challenge, then, is to predict the cognitive future of the

unborn child.

Christel Depienne and her colleagues focused on a specific

form of agenesis of the corpus callosum, isolated corpus cal-

losum agenesis, with no associated intellectual impairment.

Their study, carried out in nine different families including

four with individuals affected over several generations re-

vealed, for the first time, mutations of a specific gene called

the DCC gene, inherited in a dominant pattern. The protein

encoded by this gene allows the axons, the extensions of

neurons, to pass from one side of the brain to the other, thus

ensuring the connection between the two hemispheres: this

represents a key role in brain development.

DEFECT IN BRAIN DEVELOPMENT

DISCOVERY OF A GENE INVOLVED IN THE PROCESS

PARKINSON’S

VOLUNTARY EYE MOVEMENT, A NEW INDICATOR FOR POSTURAL CONTROL?

Unstable posture is the primary factor associated with

falling in Parkinson’s patients, however other symptoms

appear such as ocular disorders. Teams from Pitié-Sal-

pêtrière Hospital and the Brain & Spine Institute (Inserm, CNRS,

UPMC) focused on the relationship between ocular disorders in

certain patients and postural instability.

Results show that patients with postural disorders also display ab-

normal response times (latency) in voluntary eye movement. This

anomaly is correlated to a variation in parameters when initiating

a footstep, especially the length of time needed for anticipatory

postural adjustments, mechanisms implemented by the central

nervous system to maintain standing balance while executing

voluntary movements.

The study of cerebral interactions highlights extended affliction of

the mesencephalic area of the brain in the disease, involved both

in postural control and eye movements.

“ Lengthened reaction time in eye

movements, or “antisaccades”, is

a simple and reliable parameter

that could prove to be a prognostic

marker of postural control in Par-

kinson’s disease and could be used

for patient assessment in future

longitudinal studies.”

MARIE VIDAILHET (APHP, UPMC)

“ The discovery of the DCC gene

allows us to gain a deeper under-

standing of underlying causes

of corpus callosum agenesis as

well as normal and pathological

brain development. It may have

a major impact in prenatal di-

agnosis, especially in predicting

whether an unborn child will be

affected by intellectual disabil-

ity.” CHRISTEL DEPIENNE (STRASBOURG

UNIVERSITY)

Mutations in DCC cause isolated agenesis of the corpus

callosum with incomplete penetrance. Depienne C et al.

Nat Genet. 2017 Feb 27.

Antisaccades in Parkinson disease: A new marker of postu-

ral control? Ewenczyk C, Mesmoudi S, Gallea C, Welter ML,

Gaymard B, Demain A, Yahia Cherif L, Degos B, Benali H,

Pouget P, Poupon C, Lehericy S, Rivaud-Péchoux S, Vidail-

het M. Neurology. 2017 Feb 28;88(9):853-861.


ON THE CLINICAL END CREUTZFELDT-JAKOB DISEASE

A BIOLOGICAL TEST TO DETECT CREUTZFELDT-JAKOB DISEASE

Variant Creutzfeldt-Jakob Disease (vCJD) first appeared in the United Kingdom in 1996 and is linked to

the ingestion of bovine derivatives contaminated by an abnormal prion protein responsible for bovine

spongiform encephalopathy. A new wave of vCJD cases may arise in the coming years, which is why

developing a test to detect the prion agent responsible for the disease is a major public health challenge.

Thanks to research led by a research team of the French Blood Bank, in collaboration with the National CJD Sur-

veillance Network and the National Prion Reference Center (Inserm, ICM), the National Institute for Agricultural

Research and the United Kingdom’s National CJD Research and Surveillance Unit, a biological test detecting the

prion responsible for vCJD is now available.

In addition to 100% sensitivity and 100% diagnostic specificity, this test is the first to show that the prion agent

responsible for vCJD can be detected in the bloodstream before symptoms of the disease appear. Pre-sympto-

matic diagnosis of a neurodegenerative disease using abnormal protein amplification methodology is now pos-

sible with a simple blood test.

“ This test will help differentiate vCJD from other variants of the disease, evaluate prion elimination and

inactivation method efficacy, and will help study the distribution of the infectious agent in different blood

fractions. On the long term, when the test becomes automated, it may help measure the existence of disease-

causing agents in the general population.” STÉPHANE HAIK (INSERM)

Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Bougard D, Brandel JP,

Bélondrade M, Béringue V, Segarra C, Fleury H, Laplanche JL, Mayran C, Nicot S, Green A, Welaratne A, Narbey D, Fournier-Wirth C, Knight R, Will R,

Tiberghien P, Haïk S, Coste J. Sci Transl Med. 2016 Dec 21;8(370):370ra182.

FOCAL EPILEPSY

NEW TREATMENT FOR SEIZURES

Epilepsy is one of the most common neurological illnesses, with recurring seizures that can alter informa-

tion transfer by neurons. It affects roughly 430,000 individuals in France and over 50 million individuals

around the world. Several treatments are available however none are currently curative. The efficacy and

adverse side effects of anti-epileptic drugs vary from one person to the next.

Selecting initial treatment for newly diagnosed epilepsy in adults is essential and depends on a number of param-

eters: type(s) of seizures and epileptic syndrome, gender, potential pregnancy, comorbidity, co-medication…

In a stage 3 clinical trial conducted with 888 patients, Michel Baulac and colleagues proved the efficacy of lacosa-

mide alone as a first-line treatment in newly diagnosed adults with epilepsy. Additionally, it has limited side effects

and a low risk of drug interaction.

“ Many factors restrict the number of drugs adapted to a specific patient, which is why the medical community

hopes to see new monotherapy options, with a single drug, arise. These results suggest that lacosamide is a good

candidate for epilepsy treatment in newly diagnosed adult patients.” MICHEL BAULAC (UPMC / AP-HP)

Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase

3, randomised, double-blind, non-inferiority trial. Baulac M, Rosenow F, Toledo M, Terada K, Li T, De Backer M, Werhahn KJ, Brock M. Lancet Neurol. 2017

Jan;16(1):43-54.

ALZHEIMER’S DISEASE

PROGRESS IN GENETIC COUNSELING

Alzheimer’s disease is the most common form of degenerative dementia in the elderly population. Certain early

types of Alzheimer’s disease affect a minority of patients, with an onset around 50 years of age. For types, sev-

eral genes involved in the illness have been identified, including PSEN1, PSEN2 and APP. The study of mutations

of these genes amongst large populations is of immense interest in understanding early types of Alzheimer’s disease and

for genetic counseling of patients.

To further advance in this direction, ICM researchers participated in a study aimed at identifying mutations of these three

genes among families in which several members have early-onset Alzheimer’s disease and patients with early-onset Alzhei-

mer’s without any family history of the disease. PSEN1, PSEN2 and APP genetic mutations were identified in 53 new families

and 18 patients without any family history. For 10 of these patients, mutations were “de novo”, not having appeared in their

parents. PSEN1 mutations are currently screened only in familial cases, although a significant number of patients are af-

fected by the mutation “de novo”, without any family history of the disease.

Genetic counseling is an opportunity for individuals to receive precise information on the genetic cause of the illness identi-

fied within the family. In genetic illnesses that appear later in life like Alzheimer’s disease, genetic counseling allows close

family members to learn whether or not they carry the identified mutation or not.

“As a whole, this data supports the study of

PSEN1, PSEN2 and APP mutation in familial

and non-familial forms of Alzheimer’s dis-

ease. Detecting Alzheimer’s disease as early

as possible, even before its onset, could lead

to improved patient care.” STÉPHANE

EPELBAUM (APHP) AND ISABELLE LE BER (APHP)

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer

disease: A genetic screening study of familial and sporadic

cases. Lanoiselée HM, Nicolas G, Wallon D, Rovelet-Lecrux A,

Lacour M, Rousseau S, Richard AC, Pasquier F, Rollin-Sillaire A,

Martinaud O, Quillard-Muraine M, de la Sayette V, Boutoleau-

Bretonniere C, Etcharry-Bouyx F, Chauviré V, Sarazin M, le

Ber I, Epelbaum S, Jonveaux T, Rouaud O, Ceccaldi M, Féli-

cian O, Godefroy O, Formaglio M, Croisile B, Auriacombe S,

Chamard L, Vincent JL, Sauvée M, Marelli-Tosi C, Gabelle A,

Ozsancak C, Pariente J, Paquet C, Hannequin D, Campion D;

collaborators of the CNR-MAJ project. PLoS Med. 2017 Mar

28;14(3):e1002270.


ON THE STARTUP END

PARKINSON’S DISEASE

VIDEO GAMES FOR PATIENT REHABILITATION

Is it possible to develop rehabilitation for patients with Parkinson’s disease with motor and bal-

ance disorders using a video game? Apparently so, as demonstrated by the Brain e-Novation

LabCom, co-directed by Pierre Foulon from Groupe Genious and Dr Marie-Laure Welter from

the ICM, and incubated at the ICM.

In the interactive therapeutic video game designed by the team, patients are tiny animals that need

to pick up coins on a path while avoiding obstacles. To do so, they need to move in a way that en-

gages their whole body, especially axial movements: lateral movements, torso movements, etc.

The goal with this game is to increase balance and locomotive skills in patients. It comes as a com-

plementary treatment to daily medication and the usual rehab, as a symptomatic treatment.

A pilot study on 10 patients shows that their general state improved and highlighted a significant

decrease - of around 40% - in freezing when walking and fear of falling after 18 game sessions. A

joint French-Dutch project aims at studying the effects of this type of rehab on 50 patients in their

home. Online access via the www.curapy.com platform will allow therapists to communicate with

patients, follow their progress and adapt the game based on results.

A LIVING LAB PROTOTYPE

FOR INCREASED HOSPITAL PRIVACY

Getting dressed, having family over, spending quiet moments alone: all of this is impossible

in a shared hospital room. How can we improve patient well-being during long-term hos-

pital stays by increasing patient privacy?

To answer this very important question, the ICM’s Living Lab - a collaborative platform that brings

researchers, engineers, doctors, medical staff and patients together to come up with ideas and put

them into action - got together. 40 ideas were brought up, and oe of them was selected and imple-

mented in collaboration with a design school, hospital staff and patients.

The chosen solution is a mobile wall that includes a nightstand and technical supply unit (light,

oxygen, etc) to separate patients and ensure their privacy. The wall is made of wood, inspired by hos-

pitality design.

The prototype was made with external suppliers and was presented and approved by project partici-

pants. A hospital furniture supplier is willing and ready to bring the product to market.

“ Thanks to this mobile wall, patients will benefit from improved everyday life during long-term

hospital says. The Living Lab’s goal is to find the best solution for patient well-being together with

all those involved in patient care. This idea was designed and approved it ints technical, clinical

and financial aspects.” ALEXIS STEINER, LIVING LAB MANAGER

“ We hope to give all Parkinson’s patients the opportunity to use this instrument for rehabilita-

tion and therapy, at home, whenever they need. Of course, it should be used as a complement

and not a replacement for the usual course of treatment.” MARIE LAURE WELTER (APHP, INSERM),

NEUROLOGIST AND COORDINATOR OF THE BRAIN-E-NOVATION LABCOM

Dijana Nuic, et al., Rééducation par les serious games des troubles de la marche et de l’équilibre chez les patients avec maladie de

Parkinson : une étude pilote, Science Direct, Volume 46, Issues 4–5, November 2016, Pages 271–272

SEARCH, FIND, CURE, FOR YOU & WITH YOU.

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