62 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Margel Shlomo
Synthesis and Characterization of Proteinoid and Proteinoid-Polyester Polymers and Nano/Micro-Particles for Industrial and Biomedical Applications
Danielli Amos
Previously, Dr. Danielli introduced a novel technology—termed magnetic modulation biosensing (MMB)—that can rapidly detect very low concentrations of biomarkers. In the MMB system, two electromagnets are used to generate an alternating magnetic field gradients. Using these magnetic field gradients, magnetic beads with attached fluorescently labeled target molecules are aggregated and then manipulated back and forth, in and out of a fixed laser beam, generating a flashing signal, which is distinguished from the constant background noise. While the MMB system provides very high sensitivity, the electromagnets are relatively bulky and their magnetic forces are orthogonal to the gravity force. Hence, the time requires to aggregate the beads and acquire the data is long (~130 sec), which hinders the use of the MMB setup in high throughput applications. Here, we introduce a small footprint and high-throughput OMB platform. To aggregate and immobilize the magnetic beads to one spot, instead of using two electromagnets, we positioned a single cylindrical permanent magnet with a sharp tip under the sample holder. The elimination of the two relatively large electromagnets, significantly reduces the bulk, footprint, and power consumption of the platform. The use of a small permanent magnet to aggregate the magnetic beads to a small area was already reported. However, in the previous report, the small permanent magnet was positioned orthogonal to the gravity force, and therefore the aggregation time remained relatively long. In addition, the small permanent magnet was never used in combination with the preferential modulation of the laser beam, and therefore to achieve high sensitivity, multiple washing and separation steps were required. Here, the magnetic force generated by the small permanent magnet is aligned with the gravity force, significantly shortening the aggregation time of the magnetic beads from ~120 seconds to ~6 seconds. In addition, to eliminate the need for washing and separation steps, we manipulated the laser beam relative to the fixed magnetic beads. To increase the throughput of the system, we incorporated an automatic motorized linear stage that holds a 96-well plate. Shortening the aggregation, acquisition, and well to well transition times enabled us to read a 96-well plate within less than 10 minutes.
Shehadeh Naim
Reducing the conversion rate from pre-diabetes to diabetes, a personalized approach Numerous studies, such as the DPP trial, The Finnish trial, Tuomilehto et al, and the dA Qing study, have established that lifestyle modifications and weight reduction can significantly decrease the progression from prediabetes to diabetes. However, the large-scale implementation of the DPP trial faced challenges due to the recognition that a uniform approach may not be suitable for everyone, and many patients struggled to adhere to intensive consultation and follow-up. Conversely, it is important to acknowledge the “heterogeneity of treatment effects”, as treatments can vary in effectiveness among individuals (Dahabreh et al, JAMA 2023). Randomized clinical trials like the DPP can determine the overall effectiveness of treatments, but it is essential to understand which participants benefit and which do not. Treatment benefits tend to increase as an individual's baseline risk for developing diabetes increases. For instance, participants at the highest risk in the DPP trial who were randomized to metformin experienced a 22-percentage point reduction in the risk of progression to diabetes at three years compared to the control group, whereas no benefit was observed among participants at the lowest risk. Similarly, those at the highest risk who were assigned to the lifestyle intervention had a 40-percentage point reduction in the risk of developing diabetes at three years compared to Confidential-NS the control group, while the reduction among those at the lowest risk was only 8 percentage points (Sussman et al BMJ 2015). In our intervention, we have implemented a program that focuses on educating individuals about healthy eating and lifestyle habits while providing support for weight loss and increased physical exercise. To ensure adherence to treatment and engagement, we have adopted a personalized approach. This involves active involvement of the family physician and the patient in discussing and selecting the most suitable arm of intervention that aligns with the patient's specific needs and circumstances. Furthermore, we have developed and implemented practical benefit-based tailored calculators, to assess family physicians for considering the prescription of metformin and/or obesity medications: • The first calculator will assess the individual's level of risk and likelihood of responding to metformin according to ADA guidelines. • The second calculator will assess the physician regarding the suitability of the patient to get obesity medication according to his insurance company criteria. We believe that by tailoring the treatment to individual preferences and requirements, we can mitigate the risk of patient's refusal to participate and enhance engagement and reduce drop out. Preliminary data from our approach have demonstrated promising results in terms of feasibility and effectiveness (see attached abstract). To summarize, our strategy for managing prediabetes and lowering the likelihood of progressing to diabetes focuses on personalization and engagement. We recognize the diverse treatment outcomes and the significance of evaluating various risk factors while engaging in conversations with patients to assess their individual risks. By incorporating these principles into our intervention, our aim is to deliver targeted and efficient healthcare to individuals who are at risk of developing diabetes. Confidential-NS A Three arms of intervention: the personalized approach in pre-diabetic patients B Preliminary data in 505 patients (12 months follow-up) - Abstract C Calculator for medical treatment A Diabetes prevention Model see attached file B Comparing Personalized Strategies to Reduce Prediabetes to Diabetes Conversion in Primary Care Clinics Background: Randomized prevention trials show 5.8%–18.3% annual progression from prediabetes to diabetes in control arms control group (1). First-line therapy is lifestyle modification (weight loss and regular exercise) or metformin, with lifestyle change yielding the greater risk reduction. Translating evidence-based diabetes prevention strategies into routine practice necessitates adaptable, patient-centered care models. In January 2022, the northern district of Maccabi Healthcare Services implemented a prediabetes program across three cities in Northen Israel (Nof HaGalil, Shefar'am and Safed). To improve intervention adherence, this program allowed adults diagnosed with prediabetes to collaboratively select, with their physicians, one of three management pathways, including personalized consideration of metformin treatment. The three pathways were: 1) physician-led care, where management and monitoring were exclusively conducted by the primary care physician; 2) a physician care with in-person dietary counseling and nurse consultations, and 3) a remote management program, combining physician care with remote dietary counseling. We aimed to assess the short-term effectiveness of these three pathways in preventing the progression to diabetes. Methods: This retrospective cohort study analyzed anonymized electronic health record data of adults enrolled in the prediabetes program between January 1, 2022, and December 31, 2023. Baseline variables included age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), and metformin initiation status. The primary outcome was progression to diabetes within 12 months (defined as HbA1c ≥ 6.5% or two fasting glucose ≥ 126 mg/dL). Categorical variables were compared using chi-squared or Fisher’s exact tests, while continuous variables were compared using one-way ANOVA or Kruskal–Wallis tests. Results: A total of 430 out of 505 participants completed the intervention trial(85% adherence), (mean ± SD age 59.0 ± 10.9 years; 53% women; BMI 31.2 ± 6.4 kg/m²) were enrolledin the study. In the only physician-led arm (n = 130), in the physician + dietician + nurse arm (n = 212), and in the remote consultation arm (n = 88). Baseline differences were observed for age (61.5 ± 9.1, 56.8 ± 12.1, 58.2 ± 7.7 years, respectively; p < 0.001), BMI (31.2 ± 7.2, 31.8 ± 5.8, 29.2 ± 5.7 kg/m², respectively; p = 0.01), and metformin initiation rates (72.0%, 10.9%, 15.9%, respectively; p < 0.001). After 12 months, 19 participants (4.4%) progressed to diabetes: 8/130 (6.1%) in physician-led, 5/212 (2.4%) in community-based, and 6/88 (6.8%) in remote consultation arm (p = 0.12). The physician + dietician + nurse care arm showed the most effective, nonsignificant relative-risk reductions versus physician-led (RR 0.38, p = 0.08) and remote care (RR 0.35, p = 0.09); physician-led and remote pathways were similar (RR 1.11, p = 0.84). All groups had modest, comparable BMI declines. Conclusions: A personalized intervention strategy over 12 months effectively reduced the progression from prediabetes to diabetes in primary care settings, with patient adherence playing a key role. Allowing patients to choose management pathways can be beneficial in real-world practice. Larger cohorts and longer follow-up are needed to confirm the efficacy of this approach. Reference: 1. Echouffo-Tcheugui JB, Perreault L, Ji L, Dagogo-Jack S. Diagnosis and management of prediabetes: a review. JAMA. 2023 Apr 11;329(14):1206-16. C 2 calculators 1. Metformin indications 2. Obesity treatment availability in HMO’s
Banin Ehud
This research presents bio-friendly a green and cost-effective antibiofilm coating formulations based on Pickering emulsion templating. The coating does not contain any active material, where its antibiofilm function is based on passive mechanisms, laying solely on the superhydrophobic nature of the coating, and thus highly suitable for food and medical applications. The coating is based on water in toluene or xylene emulsions that are stabilized by commercial hydrophobic silica, with Polydimethylsiloxane (PDMS) that is dissolved in the organic phase. The stability of the emulsions and their structure were studied by confocal microscopy. The most stable emulsions were applied on polypropylene surfaces and dried in an oven to form PDMS/silica rough coatings. The surface morphology of the coatings shows a honeycomb-like structure that exhibits a combination of micron-scale and nano-scale roughness resulting in a superhydrophobic property. The superhydrophobicity of the resulting coatings has been tuned to meet the demands of highly efficient antibiofilm passive activity. The obtained coatings have shown to significantly reduce the accumulation of a decrease of one order of magnitude in the EEscherichia coli-coli accumulation on the surface, suggesting these coatings can be used for antibiofilm applications. that is a significant value for coating with a passive based antibiofilm coating.
NESSIM GILBERT
Osteoarthritis (OA) is a major burden that affects ~ 40 million of EU citizens, with enormous direct and indirect costs for the European healthcare systems, quantified in ~ 50.4 billion euros per year. This disease involves the degeneration of cartilage and other joint structures and is one of the most common causes of pain and disability in middle-aged and elderly people. ADMAIORA aims in the long-term at increasing the healthy and active lifespan of people affected by OA, by considerably slowing down or even stopping the degeneration process, thus delaying or avoiding surgical interventions for total joint replacement. Within the project time-frame the target is to achieve a 60% reduction of degeneration in OA animal models treated with the ADMAIORA technologies, with respect to control (untreated) ones, after 4 weeks, and a 90% reduction after 3 months. To achieve this ambitious objective the Consortium will evolve and merge technologies that already showed a high potential as experimental proof of concepts (TRL = 3) and will bring them at a preclinical level (TRL = 5). The ADMAIORA Consortium will develop biosynthetic hydrogels embedded with carbon-based nanomaterials, conferring higher mechanical and lubrication properties, and piezoelectric nanoparticles enabling responsivity to remote wireless ultrasound waves. Stem cells derived from autologous adipose tissue, which already demonstrated anti-inflammatory and regenerative properties, will be entrapped in the hydrogels. Materials and cells will be delivered in situ through an innovative handheld 3D bioprinter, embedded in an arthroscopic tool. A custom brace will be designed and equipped with ultrasound probes for both monitoring the joint status and stimulating the implanted piezoelectric nanobiomaterial. A dedicated App will allow a direct connection between patient and physician in an Internet of Things framework. Overall, ADMAIORA will target a ground- breaking paradigm that may revolutionize OA treatment.
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.
Gerber Doron
Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell-based testing. Herein, presented is a microfluidic device that combines a drug microarray with cell microscopy. The device can perform 512 experiments to test chemosensitivity and resistance to a drug array. MCF7 and 293T cells are cultured inside the device and their chemosensitivity and resistance to docetaxel, applied at various concentrations, are determined. Cell mortality is determined as a function of drug concentration and exposure time. It is found that both cell types form cluster morphology within the device, not evident in conventional tissue culture under similar conditions. Cells inside the clusters are less sensitive to drugs than dispersed cells. These findings support a heterogenous response of cancer cells to drugs. Then demonstrated is the principle of drug microarrays by testing cell response to four different drugs at four different concentrations. This approach may enable the personalization of treatment to the particular tumor and patient and may eventually improve final patient outcome.
Cohen Cyrille
This is an optimized BCMA-specific chimeric antigen receptor for the treatment of multiple myeloma and other hematological diseases that we have developed.
Fischer Bilha
The detection of subcellular domains in cells can be obtained by specific fluorescent markers. Here we report the use of styryl quinolinium dyes that selectively stain ribosomal RNA (rRNA) in nucleoli and in the cytoplasm of mammalian cells. Specifically, we synthesized a series of 1-methyl-4-(substituted) styryl-quinolinium derivatives, 12a–l. We developed highly efficient microwave-assisted synthesis which prevents the formation of side products, leading to the products in yields greater than 90%. Compounds 12c-f and 12i in various solvents exhibited maximum absorbance at 500–660 nm, molar extinction coefficient of 25400–49000 M
Cohen Cyrille
TGFβ is a major immunoinhibitory factor present in the microenvironment of solid tumors. Different cancer types acquire the ability to overexpress TGFβ to escape immune response. Indeed, TGFβ dampens cytotoxic T cell activity, and its presence has been shown to correlate with tumor invasion and poor prognosis. Herein, we developed two approaches to target the effects of TGFβ and provide a functional advantage to genetically engineered T cells in the immunoinhibitory tumor milieu. We designed a TGFβRI-based co-stimulatory switch receptor (CSRI) that includes the TGFβ receptor I extracellular binding domain and a 4-1BB co-stimulatory signaling moiety. Additionally, we tested the function of a TGFβ-binding scFv trap produced by T cells. We demonstrated that both approaches endowed tumor-specific T cells with superior cytokine secretion, upregulation of activation markers, and reduced expression of inhibition markers upon co-culture with melanoma targets. Moreover, we noted that CSRI and the anti-TGFβ trap showed an improved anti-tumor function in vivo. Overall, we show that it is possible to target the TGFβ pathway to improve cellular immunotherapy.
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.
