Conference Program

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Minister of Science and Technology, Israel

Chief Scientist and Chairman, Israel Innovation Authority

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Weebit nano, Teramount, prior Vice President and Chief Product officer of Intel Corporation, Israel

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel


Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Weebit nano, Teramount, prior Vice President and Chief Product officer of Intel Corporation, Israel

Chief Scientist and Chairman, Israel Innovation Authority

Weizmann Institute of Science, Israel

Tel Aviv University, Israel
Background
There are known genes which may lead to autism syndromes, with lead genes including CHD8 and SHANK3, and the ADNP gene. Discovered in the Gozes laboratory, the activity-dependent neuroprotective protein (ADNP) gene is one of the most prevalent mutated genes within the autism spectrum disorders (ASDs), leading to the ultra-rare syndrome, the ADNP syndrome. Over 400 genes are regulated by ADNP, which are critical for brain formation, organ development, cognitive and motor functions
Objective
Understand the ADNP syndrome and develop personalized treatment
Methods, Results and Conclusions:
The ADNP syndrome occurs when one of the two copies of the ADNP gene is mutated, mostly de novo resulting in loss of normal functions. Original data showed that Adnp+/- mice suffer from learning and memory deficiencies, muscle weakness, and communication problems. Further studies showed that the ADNP microtubule (MT)- interacting fragment NAP (drug candidate -CP201, also discovered in the Gozes laboratory) resolves, in part, Adnp deficiencies and protects against ADNP mutation abnormalities. With a clean toxicology profile and positive human adult clinical trial experience, CP201 is planned for future clinical trials in the ADNP syndrome.
Selected recent publication:
Grigg I, Ivashko-Pachima Y, Hait TA, Korenková V, Touloumi O, Lagoudaki R, Van Dijck A, Marusic Z, Anicic M, Vukovic J, Kooy RF, Grigoriadis N, Gozes I. Tauopathy in the young autistic brain: novel biomarker and therapeutic target. Transl Psychiatry.

University of Santiago de Compostela, Spain

Hadassah University, Israel

Weizmann Institute of Science, Israel

University of Santiago de Compostela, Spain

Tel Aviv University, Israel

Restorative Neurotechnologies, Italy
We previously discovered that adaptation to visuomotor distortion induced by prismatic lenses increases activation of the brain ipsilateral to the deviation, thus modulating cognitive functions associated with that hemisphere. We developed a device, Mindlenses, composed by prismatic lenses integrated with a web platform recording neuropsychological data and with an application that allows digitalization of the prismatic adaptation procedure, in which the subject points to a series of lateralized visual targets presented on a tablet’s screen. The application also contains serious games specifically designed to be executed while wearing the lenses, according to the specific cognitive function to be modulated.
We present the results of a 10day session of treatment using this device on a sample of 10 patients with first ever unilateral stroke (5 right and 5 left ischaemic stroke patients, mean age 76, SD 4.2 years). Prismatic lenses were applied so as to induce a deviation of the visual field ipsilateral to the lesioned hemisphere. Patients were tested on both the cognitive functions specifically dependent on the lesioned hemisphere and on those associated with the contralesional hemisphere. Digitalized tests targeting the left hemisphere were digit span, forward and backward, verbal supraspan, phonological fluency, recognition memory task for words.
Digitalized tests targeting the right hemisphere were spatial span, forward and backward, spatial supraspan, recognition memory for faces and buildings.
Tests were performed before the treatment and after a 10 days session of treatment with Mindlenses. Average scores of the tests at the two time points were compared using paired t-test.
We found a significant improvement of the cognitive tasks associated with the hemisphere modulated by Mindlenses (p = 0.02). The cognitive tasks associated with the hemisphere not modulated by Mindlenses were unaffected by the treatment (p > 0.05), thus confirming the specificity of the effects.
These results document clinically a significant modulation of cognitive performance following application of a tool that integrates visual distortion with serious games targeting the hemisphere affected by focal stroke.

Effectivate, Israel
Background:
Natural age-related cognitive decline influences basic functions such as memory and attention and has adverse effects on seniors’ wellbeing. As life expectancy increases, more individuals experience this phenomenon, resulting in a critical mass of people looking for a solution for preserving cognitive abilities.
Extensive research was done testing the effectiveness of computerized cognitive-training, and recently large meta-analysis concludes cognitive training can be beneficial.
Building upon scientific findings, Effectivate, used cutting edge technology and design to create the next generation of computerized training, addressing the unmet needs of older adults.
Objective:
Examine the influence of “Effectivate”, a self-administered cognitive-training application, on seniors` attentional and memory functions.
Methods:
Data was collected from 275 random “Effectivate” users (ages 67.58, ±8.13) at baseline and after 6-7weeks of training with the Effectivate protocol. Attentional and memory functions were assessed using a built-in battery including well-known tasks.
Results:
Processing speed: overall improvement was observed with greater improvement in older participants (t(136)=2.27, p<0.05); Object-location binding: an overall increase in accuracy was found under high visual load (t(274)=1.70, p<0.05); Attentional control: a significant decrease in RTs was found in, for participants with longer training durations (t(135)=6.30, p<0.001).
Conclusions:
The results imply that the “Effectivate” protocol may support older adults’ cognitive state.
These support the findings of another recent study led by Prof. Ben-David, with preliminary results show improvement in cognitive abilities and far-transfer in healthy community-based seniors.

CVAID Medical, Israel

QuantalX NeuroScience, Israel
Brain disorders account for 35% of all health-related economic burden. This enormous challenge increases as world population continues to grow due to rise in life span and with it the age-related brain disorders such as Cerebral Small Vessels Disease (CSVD), stroke, mild cognitive impairment (MCI) and dementia, etc.
90% of strokes and 35% of dementias have been estimated to be preventable if detected at an early enough, enabling efficient medical intervention.
However, current diagnostic tools lack the sensitivity and objectivity needed for early and accurate diagnosis, leading to under-diagnosis at extremely late stages that might already be untreatable. Thus, there is an obvious need for a fast, easy-to-use, low-cost, objective, and sensitive test that will enable the diagnosis of brain function abnormalities at the very early, pre-pathological, physiological stage of deterioration.
Electroencephalography (EEG) and Transcranial magnetic stimulation (TMS) have been employed extensively in clinical research and provide a non-invasive, direct and reliable solution for objectively measuring brain function.
DELPHITM is the first system that provides physicians with real-time, objective and patient independent assessment of brain function. DELPHITM operates a combination of TMS and EEG devices with unique algorithms to measure well-characterized physiological properties of brain function of connectivity and plasticity in specific brain networks such as cortico-spinal network, fronto-parietal network, inter-hemispheric connections and visual network.
DELPHITM is easily integrated into any clinical setting for routine brain health evaluation or emergency medicine. DELPHITM aids the physicians diagnosis by providing valuable insights into their patient’s brains health while saving the healthcare system a significant percent of clinical assessment and diagnosis costs. The physician may utilize these biomarkers to detect early brain degeneration conditions, perform a differential diagnosis and determine an optimal personalized treatment.

University Hospital Reims, France

University of California, Los Angeles, USA

University of California, Los Angeles, USA
Neural repair is a therapeutic strategy distinct from acute stroke strategies such as reperfusion: biological targets are different, the goal is to boost function in surviving brain elements rather than salvage threatened tissue, and time windows are measured in days-to-weeks rather than hours. Many classes of therapy are under study in animals and in human trials to improve stroke recovery including cellular therapies, monoclonal antibodies, drugs, electromagnetic brain stimulation, devices, and telehealth-based therapies. Some of these repair-based therapies are introduced days-to-weeks post-stroke, to amplify innate repair mechanisms, while others are offered months-to-years post-stroke, to help foster new brain plasticity. This lecture will review many of these therapeutic approaches that are currently under study. We will also consider principles of neural repair, which are important to maximizing the benefit from restorative therapies after stroke.

Shaare Zedeck Medical Center, Israel

Hadassah-Hebrew University Medical Center, Israel

University Hospital Reims, France

University of California, Los Angeles, USA

University of California, Los Angeles, USA

President, Israeli Headache Association

Calcitonin gene-related peptide (CGRP) is a ubiquitous neurotransmitter found all over the central and peripheral nervous system. It is a vasodiIator and it increases pain transmission. It is thought to be especially critical in the trigemino-vascular system, in the 1st division of the trigeminal nerve, from the trigeminal ganglion to the periphery of that nerve. CGRP levels are elevated during a migraine attack and giving a triptan lowers the levels and improves the patient. Giving IV CGRP causes a headache in migraine patients and often a delayed migraine attack. We now have 6 products that block GCRP’s effect and improve migraine, 4 injectables and 2 oral products.
Four are monoclonal antibodies available in the US for prevention of migraine (one is also approved for Cluster headache prevention). Two are gepants, which are small molecule CGRP receptor blockers are approved for the acute care of migraine. One of those will also be used for prevention. A third gepants will only be used as a migraine preventive.
There are 4 more acute care treatments for migraine that will be discussed, all composed of available medications that have either been combined or given via a different route of administration.
There is one new medication that acts something like a triptan by stimulating the 5-HT1F receptors and does not constrict blood vessels.
Finally, there is an old medication that is no longer in use due to adverse events, which has been re-engineered to no longer have those AEs. This is exciting as it was our favorite preventive oral tablet for migraine and cluster headache.

Rabin Medical Center, Israel


President, Israeli Headache Association

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Geffen School of Medicine at UCLA, USA

Institute of Biomedicine of Seville, Spain

University Hospital Center of Montpellier, France

Hadassah-Hebrew University Medical Centers, Israel

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Institute of Biomedicine of Seville, Spain

University Hospital Center of Montpellier, France

Hadassah-Hebrew University Medical Centers, Israel

Rabin Medical Center, Israel

Geffen School of Medicine at UCLA, USA

Tel Aviv Sourasky Medical Center, Israel

Hadassah-Hebrew University Medical Center, Israel

Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel

Tel Aviv Sourasky Medical Center, Israel

Hadassah-Hebrew University Medical Center, Israel

Tel Aviv University, Israel

Tel Aviv University, Israel

Alpha Omega, Israel

Rabin Medical Center, Israel

Hebrew University and Hadassah Medical Center, Israel

Tel Aviv University, Israel

Tel Aviv University, Israel

Soroka Medical Center, Ben Gurion University, Israel
Tele-neurology, the practice of delivering medical care to patients suffering from neurological conditions without a physical encounter, was until recently, widely used in the context of acute stroke care, but hardly used in other fields of Neurology. The Covid-19 pandemic has forced patients and neurologists to use digital platforms, especially video teleconferencing technologies, and many have adapted quickly to the new reality yet the practice of tele-neurology still face major challenges, providing opportunities for developers and entrepreneurs.
Besides the general challenges of tele-medicine (difficulties in achieving effective and emotional communication with on digital platforms), Neurologists struggle with difficulties in preforming neurological examination and evaluating cognitive abilities.
This challenge opens the way for alternative digital approaches allowing the neurologist to gain insights on their patients, by using patient operated devices, analysis of data from smart personal or home systems, digital cognitive assessment batteries and even by extracting video clips from security cameras.
The development of comprehensive remote testing toolkits, compatible with the Neurologist work flow, can utilize existing technologies currently used in the worlds of gaming, prosthetics and homeland security. Such toolkits, deployed in neurological services as decision support aids, may eventually serve as diagnostic tools as data sets become more extensive.

Rush University Medical Center, USA

University Hospital Kiel, Germany
Mobile health technologies are developing extremely fast and provide new means for measuring everyday situations and behavior practically every day. They are conquering the sports and fitness market and represent a globally relevant economic factor. Due to the accuracy of the measurements, and because this data can be collected in the domestic environment practically without time limit, this development is also very interesting for the medical field. Mobile health technologies that assess motor and mobility performance are specifically advanced and are therefore particularly interesting for the recording of symptoms in movement disorder. In fact, a first endpoint for the measurement of mobility in a movement disorder (fastest walking speed in everyday life in Duchenne Muscular Dystrophy) has already been approved by a regulatory body (European Medicines Agency, EMA). This talk presents concepts, designs, and validation strategies in the development of mobile health technologies-derived parameters for movement disorders, and discusses their potential and challenges. Specific assessment strategies are presented, specifically out of the performance, perception and capacity fields. The presentation will also provide an impulse for the design of future assessment protocols in observational studies and clinical trials, so that the understanding of these novel parameters can grow rapidly. Ultimately, this requires intensive collaboration between the various stakeholders, including patients, medical professionals, industry, regulatory bodies, and politics.

Tel Aviv Sourasky Medical Center, Israel

Soroka Medical Center, Ben Gurion University, Israel

Rush University Medical Center, USA

University Hospital Kiel, Germany

Sheba Medical Center, Israel
Cognitive dysfunction is now recognized as complication of diabetes. People with diabetes have a 1.5-2 fold greater risk for age related cognitive decline, 1.4-1.8 greater risk for MCI, 1.5-2 fold greater risk for AD, 2-2.5 fold greater risk for vascular dementia. The cognitive domains that are effected are the same ones that are effected by age: psychomotor efficiency, learning, memory & executive function. The relationship between diabetes and cognitive dysfunction has several implications: 1. self care ability, a corner stone of diabetes treatment may be impaired in people with cognitive dysfunction. Hence, current recommendation of many diabetes professional organizations to conduct screening & surveillance of cognitive function & to tailor treatment plan accordingly; 2. second, it is important to understand the effect of glucose lowering pharmacological agents on diabetes related cognitive dysfunction.3.third, it may well that understanding the effect, may allow extrapolation for use in people without diabetes.
Glucagon like peptide (GLP) – 1 is a hormone secreted by the intestine. GLP-1 & GIP constitute the incretin hormones that potentiates the synthesis and release of insulin in a glucose dependent manner ( the incretin effect that is blunted in people W type 2 diabetes). GLP-1 receptor agonists (RA) are a widely used class of drugs in people with diabetes. According to current guidelines they are prescribed as the first injectable & 1st line therapy for glucose control after Metformin & life style. GLP-1 RA differ in their structure and duration of action and have been studied in CVOTs of varying sizes and with different patient populations with a 12% reduction in MACE composite (non fatal stroke, MI, CV death). The effect seems to be even more pronounced with respect to stroke prevention – with a statistically significant and homogenous reduction of 16% in stroke in a recently published systematic review.
Basic science models suggest a neuroprotecitive effect of GLP-1 RA. GLP-1R are found in many brain related to memory and learning & not connected to metabolic control ( ex. dentate gyrus), on glial cells. Studies have shown that mice KO for GLP-1R exhibit impairment in contextual memory reversible after GLP-1R gene DNA transfer. In mice with high fat dietary induced obesity & insulin resistance Liraglutide treatment induced an improvement in learning & memory ability. Data from recent months also suggests a similar effect in human studies. Thus, in a post hoc analysis of 3 randomized controlled trials including 15820 individuals with type 2 diabetes treatment with Liraglutide/Semaglutide compared to standard of care reduced incident dementia rate (collected as AE). In the recently published cognitive sub study of the REWIND trial treatment with Dulaglutide vs. standard of care reduced incident country standardized baseline adjusted substantive cognitive impairment by 14%. GLP-1 RA have also been tested in small studies in people without diabetes with AD/MCI, Parkinson’s disease and mood disorders with initial promising results.
To Conclude: Cognitive dysfunction is a less recognized complication of diabetes that is becoming increasingly important in light of the high numbers of older people with diabetes. Evidence from the last several years suggest a neuroprotective effect of the GLP-1 RA. Recent evidence from several randomized controlled trials in people with diabetes demonstrate a robust effect on stroke and a possible effect on cognitive dysfunction. Larger studies with cognitive dysfunction as the primary outcomes are needed.

Sheba Medical Center, Israel

Rambam Health Care Campus, Technion- Israel Institute of Technology, Israel

Sheba Medical Center, Israel

Sheba Medical Center, Israel

Hebrew University and Hadassah Medical Center, Israel
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) for human patients with Parkinson’s disease (PD) is a success story. By now more than 200,000 PD patients have received STN DBS in ~1000 centers around the world. Nevertheless, only ~25% of PD patients eligible for DBS will have the procedure, and DBS is seldom applied for other brain disorders.
In my talk, I will try to depict the barriers for DBS and to outline our efforts to minimize the duration, cost and patient discomfort during DBS procedures and post-operative treatments, as well as our efforts to maximize the benefits of the procedure.
To do so, I will describe our electrophysiological studies in human patients undergoing DBS procedures and in non-human primates before and after induction of basal ganglia related disorders by MPTP (PD) and PCP (schizophrenia). I will describe our methods for automatic navigation to DBS targets, even under mild sedation. Finally, I will outline our suggested strategy for closed-loop adaptive DBS for PD, and will report of our early-stage efforts (or delusions) to treat the negative symptoms of schizophrenia by closed-loop DBS of the non-motor domains of the STN.