The Virtual Congress on

Brain Health

Innovation & Technologies

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.

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.

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.

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.

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.

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 1^st 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-HT_1F 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.