16 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Keshet Joseph
Speech sound disorder is a communication disorder in which children have persistent difficulty saying words or sounds correctly. Speech sound production describes the clear articulation of the phonemes (individual sounds) that make up spoken words. Speech sound production requires both the phonological knowledge of speech sounds and the ability to coordinate the jaw, tongue, and lips with breathing and vocalizing in order to produce speech sounds. Most children can say almost all speech sounds correctly by the age of 4 years old. A child who does not pronounce the sounds as expected may have a speech sound disorder, which may include difficulty with the phonological knowledge of speech sounds or the ability to coordinate the movements necessary for speech. These communication difficulties can result in a limited ability to effectively participate in social, academic, or occupational environments. Overall, 2.3% to 24.6% of school-aged children were estimated to have speech delay or speech sound disorders (Black, Vahratian, & Hoffman, 2015; Law, Boyle, Harris, Harkness, & Nye, 2000; Shriberg, Tomblin, & McSweeny, 1999; Wren, Miller, Peters, Emond, & Roulstone, 2016). Children with speech sound disorder are referred to speech therapy, that usually takes around 15 weeks. At first the clinician works with the child on an auditory diagnosis for the distorted sounds at different levels (a sound, a syllable, an expression and a single word). Next, the work is focused on learning the motor skills of sound production and on the location of the articulator organs during the production using visual feedback in addition to auditory feedback. Many research papers show that the most critical part of the treatment is the feedback given to the patient, which helps her or him to develop a correct model of pronunciation.
Schiff Rachel
We utilize AI techniques (deep learning, computer vision) to assess motor visuospatial gestalt and memory abilities. Using a shape reproduction task and analyzing the gap between the original and reproduced shape, such tools enable a robust, reliable and accurate assessment. Moreover, modern tablet technology enables the algorithm to reach a level of accuracy unmet by human diagnosticians.
Shai Rahimipour
β-Sheet aggregation between amyloid proteins is a key trait of neurodegenerative conditions, such as Alzheimer’s (AD) and Parkinson’s disease (PD), having dire socioeconomic consequences. In the US alone, AD effects 5.7 million Americans and costs $277 billion/year, a burden due to increase over the next 10 years. Without a cure, FDA approved drugs for AD and PD treat only symptoms. The current invention describes novel Aza-cyclopeptides that are based on our previously discovered and patented cyclic D,L-
Albeck Amnon
Development of new synthetic compounds that prevent the autistic symptoms and improve some brain biochemical factors that are associated with autism
Shai Rahimipour
Drug delivery systems play a crucial role in optimizing drug therapy by improving drug efficacy, reducing side effects, enabling targeted delivery, and overcoming biological barriers. They also contribute to advancements in personalized medicine and have the potential to revolutionize healthcare by enhancing treatment outcomes and patient compliance. The advances in genome mapping, molecular diagnosis and production of highly selective humanized antibodies enable the development of precision medicine. Moreover, the emerging technologies in mRNA-based vaccines and treatments together with the breakthrough in gene manipulation using the CRISPR/Cas9 editing methodology have open new avenues in discovery of novel drugs. In general, the translation of these advances into successful therapies relies on the use of biologics, including peptides, proteins and oligonucleotides that exhibit high specificity and potency. However, delivery of drugs and biologics into the brain in different central nervous system conditions, such as Alzheimer’s disease (AD) and Parkinson’s disease, glioblastoma and stroke, remains still a highly challenging endeavor, due to the blood-brain barrier (BBB). Therefore, there is a growing need for small, non-toxic, and affordable molecules that can increase the penetration of biologics and nanoparticles (NPs) carriers through the BBB. In this application, we demonstrate successful delivery of biocompatible liposomes and gold nanoparticles (GNPs) through BBB by systemic (i.p. and i.v.) injection for early diagnosis and therapy of AD. We show that conjugation of non-BBB permeable gold nanoparticles (GNPs) and liposomes with a cell permeable cyclic D,L-a-peptide (CP-2) dramatically increase the BBB permeation of the particles to generate theranostic probes for early diagnosis and therapy of AD. Targeting the oligomeric forms of Aβ in brain, Aβ oligomers and plaques were detected in the well-established 5xFAD mouse model of AD by CT and fluorescent imaging as early as 2-months. In transgenic Caenorhabditis elegans AD models overexpressing human Aβ, CP-2-conjugated NPs significantly outperformed free CP-2 by improving cognitive and behavioral functions, extending lifespan through reducing toxic Aβ oligomer levels.
Cohen Haim
Mice overexpressing Sirt6 or fed a caloric restriction (CR) diet live longer with improved health. CR increases Sirt6 levels and its beneficial effects are mediated by the gasotransmitter H2S, a one-carbon pathway product. Yet, the role of this pathway in Sirt6-regulated longevity remains elusive. Here, we show that Sirt6 controls hepatic one-carbon metabolism, specifically preventing the aging-dependent H2S reduction, and elevation of the methyl donor, SAM. Sirt6-dependent acetylome analysis of old liver revealed differential acetylation of most of the one-carbon enzymes. Sirt6-dependent Matα1 K235 deacetylation reduces SAM production activity and Cbs binding, thereby reducing its activation of Cbs-dependent H2S production. In addition, Sirt6 downregulates xCT expression in a Sp1-dependent manner, decreasing cystine uptake and increasing Cgl H2S production activity. The net outcome is H2S and SAM levels similar to those observed in young animals. Thus, we unveil a fundamental mechanism for the promotion of healthy longevity by Sirt6.
Mandel Yossi
A device and system for storing and maintaining the viability of an enucleated eye globe ex vivo. The device includes a part-spherical eye bed designed to support the globe and integrate with a perfusion system for nutrient and oxygen delivery. Retinal functionality is monitored using electrophysiology by recording electroretinogram (ERG) signals, providing a robust measure of tissue viability and preservation quality for preclinical testing or potential transplantation.
Mandel Yossi
The invention is a new device and method that enables a better interface between electrodes and patients’ (or other) neural tissue, such as the retina. The invention is based on high-density electrode array integrated with glutamatergic (or other) cells. Upon implantation of the device into the subretinal space of patients suffering from retinal degeneration (e.g.; age-related macular degeneration) the neurons synapse with the host retina. Activation of individual neurons by electric field elicits activation of the host retina with natural characteristics and restores vision at resolution and quality near normal vision.
Polat Uri
Network activity within the brain in the gamma frequency (30–100Hz) plays an important role in information transfer across connected brain regions and across cortical hemispheres. Such oscillatory activity brings multimodal inputs together in a target region for efficient spatio-temporal integration. The gamma-frequency oscillation was shown to slow down lose power in mouse model of Alzheimer’s Disease. Transcranial alternating current stimulation projecting Gamma waves was shown to positively affect the long-lasting enhancement of synaptic transmission in mice models of Alzheimer’s Disease. In the invention a new method is provided for increasing a user’s cognitive ability/abilities, the method comprising presenting to the user one or more visual training-tasks, via processor implemented method steps of displaying, at least one session (S1, S2…), each session of KS visual training-tasks, requiring the user’s one or more responses; whereby the visual training-tasks are configured to induce a long-term amplification of the brain’s frequency power, in reaction to at least the provided visual training-tasks, thereby increasing at least one of the user’s cognitive abilities.
alon shahar
We present a method for multiplexed RNA and protein detection in intact, thick organoids. Organoid thickness represents a major barrier to in situ molecular analysis. Our approach extends Expansion Sequencing (ExSeq)—previously limited to tissue sections up to ~50 µm—to organoids ranging from 100 µm to 300 µm in diameter. Importantly, organoids exceeding 300–500 µm frequently develop necrotic cores due to restricted oxygen and reagent diffusion, making 300 µm a practical upper limit for intact, physiologically relevant analysis. A key innovation of this method is delayed hydrogel polymerization, which enables uniform diffusion of gel monomers throughout the tissue prior to crosslinking. Additional challenges, including limited surface area, enzyme penetration, and imaging depth, were addressed through automated pipetting, glass-slide embedding, and protocol optimizations (Table). By physically expanding whole brain organoids within a hydrogel matrix, this method enhances spatial resolution by up to ~10× and allows iterative rounds of antibody staining and in situ RNA sequencing in the same sample. While demonstrated in neurodevelopmental organoid models such as STXBP1 encephalopathy, this platform is broadly applicable to diverse organoid systems for 3D multimodal molecular profiling.
Yadid Gal Moshe
Synthetic delta receptor peptide agonists as a new treatment for cocaine addiction and pain.
Okun Eitan
Down Syndrome (DS), which results from a trisomy of chromosome 21 (Hsa21), is the most prevalent genetic cause of intellectual disability worldwide1-3. Some genes on the human chromosome 21 are highly correlated to Alzheimer's disease (AD) pathogenesis, including the amyloid precursor protein (APP), which is overexpressed in individuals with DS, causing early-onset AD (EOAD)-related neuropathology4-6. Furthermore, an alarming association was found between pregnancy with a DS-affected fetus and a 5-fold increased risk of mothers developing late-onset AD (LOAD) later in life, compared with pregnancies with fetuses affected by other forms of intellectual disability7,8. We suggest that fetomaternal transfer of APP and its proteolytic fragments occurs during pregnancy with a DS fetus and that these fetal factors infiltrate the maternal central nervous system, contributing to Aβ-seeding in the maternal brain, adversely affecting their cognitive abilities. By modeling DS-like pregnancies in mice, by mating of wild-type (WT) female mice for 4 consecutive pregnancies with mouse strains that overexpress the human amyloid precursor protein (hAPP) during early embryonic stages, we have observed fetal DNA, mRNA, proteins, and cells in the mothers' brains and periphery tissues following pregnancies, resulting in maternal cognitive decline. To delay the observed cognitive decline resulting from the transfer of neurotoxic peptides, we have generated a novel vaccine specific for the human neurotoxic N-terminal epitope of APP, the N-APP (APP108-113) fragment, which we observed to reside in the periphery of Aβ plaques in the brain of EOAD mouse brains and present in the brains of mothers to hAPP-expressing mouse fetuses. Vaccinating WT female mice with the N-APP vaccination prior to their exposure to hAPP-expressing fetuses improved short-term memory abilities in several behavioral assays and may therefore be helpful as a preventative treatment for maternal cognitive decline following DS pregnancies. In addition, vaccinating 5xFAD mice, which model EOAD, with the N-APP vaccine, improved cognitive measures in various cognitive tasks.
