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Technology Name
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Scientist
1665
Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes....

Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.
Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes. Hypertension and diabetes elicit fibrotic processes in the heart, placing a high percentage of the western world population at risk, yet the early identification of fibrotic development in high-risk patients is hindered by lack of adequate fibrosis imaging modalities. This in turn leads to increased morbidity and additional financial burden to health care services. The current standard method to assess myocardial fibrosis employs the usage of MRI coupled with intravenous infusion of Gadolinium contrast agent. However, this method suffers from considerable drawbacks including reduced sensitivity (that permits diagnosis only at advanced stages of disease), lengthy scan times and toxicity of the contrast agent, which excludes a significant subset of patient populations from diagnosis. Thus, the capacity to diagnose myocardial fibrosis in its early stages would allow successful therapeutic intervention, and may also create a platform for the non-invasive study of fibrotic development, thereby facilitating the design of targeted therapies. The current invention is comprised of a novel cardiovascular magnetic resonance method with enhanced sensitivity, without the need for contrast agent administration.

Applications


  • Detection of cardiac fibrosis due to various pathologies, including hypertension, diabetes and heart failure.
  • The method can be applied to detect fibrotic tissues in a broad range of disorders including cancer, renal fibrosis and pathologies related to skeletal muscles.
  • A platform for the clinical study of targeted therapies that may prevent or arrest fibrotic diseases.
  • Monitoring the efficacy of treatment tailored to target fibrotic tissue development.

 


Advantages


  • The method relies on magnetization transfer to provide contrast, and therefore obviates the need for any extrinsic, toxic contrast agent such as Gadolinium.
  • Improved sensitivity over current contrast agent-based cardiac MRI methods.
  • The method can be readily applied to existing MRI clinical imaging systems.

Technology's Essence


A team of researchers at the Weizmann Institute has developed a novel approach for detection of myocardial fibrosis using magnetization transfer contrast (MCT) MRI cardiac imaging technology. The method was tested in vivo on animal models of heart failure and proved highly sensitive for detection of scar tissue formation and monitoring of fibrotic development. One prominent advantage of the present technology over current cardiac imaging modalities is that it eliminates the requirement for extrinsic contrast agents, thereby circumventing potential adverse toxic side effects.

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  • Prof. Michal Neeman
1801
A new image processing tool for transient detection was developed by the group of Prof. Gal-Yam, originally for time-domain observational astronomy.Image sequences are used in various fields, including medical imaging and satellite/airborne imaging. The comparison between images taken at different...

A new image processing tool for transient detection was developed by the group of Prof. Gal-Yam, originally for time-domain observational astronomy.
Image sequences are used in various fields, including medical imaging and satellite/airborne imaging. The comparison between images taken at different conditions (e.g. equipment or configuration, angles, weather and wavelength) can be a highly non-trivial problem, as subtraction artifacts can outnumber real changes between images.
The existing remedy for this problem includes highly complex solutions using machine learning algorithms to narrow the sea of candidates. In some cases, human interpretation of images cannot be avoided, resulting is very long processing times.
The new method presented here provides a proven solution for the subtraction of images taken at varying conditions. The tool can be applied for any type of imaging, allowing fast processing and accurate results.

Applications


  • Satellite/airborne imaging

  • Medical imaging
  • Defect detection

Advantages


  • Fast and automatic

  • Generic, can be applied to various imaging scenarios
  • Easily implementable into existing systems

Technology's Essence


The new method is used for processing at least two N-dimensional data-measurements (DMs) of a physical-property for detecting one or more new-objects and/or a transition of one or more known-objects, in complex constant-background DMs. Generally, the

the method includes: (1) generating a filtered-new-DM by match-filtering a new-DM, respective to impulse response of a reference-DM (2) generating a filtered-reference-DM by match-filtering the reference-DM, respective to impulse response of the new-DM (3) generating an N-dimensional object-indicator (OI) by subtracting the filtered-reference-DM from the filtered-new-DM, or vice versa and (4) generating an N-dimensional data score from the N-dimensional OI, where each of the scores is a probe for existence of an object at a specific N-dimensional location.
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  • Prof. Avishay Gal-Yam
1712
  • Prof. Yechiel Shai
1752
Heart failure is the leading cause of death in the western world. Existing treatments fail to compensate the irreversible loss of functional cardiomyocytes (CM), thus presenting a major medical unmet need. Inducing native CM replacement is one approach being tested as regenerative treatment, with the...

Heart failure is the leading cause of death in the western world.
Existing treatments fail to compensate the irreversible loss of functional cardiomyocytes (CM), thus presenting a major medical unmet need. Inducing native CM replacement is one approach being tested as regenerative treatment, with the advantage of a more straightforward methodology over cell transplantation approaches. 
In a multidisciplinary study, headed by Prof. Eldad Tzahor from the Weizmann institute of Science, the tyrosine kinase ERBB2 was shown to be both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
Thus, potentiation of ERBB2 signalling in adult CMs might represent a promising therapeutic approach for CM replacement in heart failure.

Applications


  • Induction of cardiomyocytes replacement therapy following heart injury.

Advantages


  • Straightforward methodology – Avoids complications associated with the requirement for cell transplantation.
  • Include several optional targets - both ERRB2 and its downstream effectors serve as potential targets for therapeutic agents, which may be administrated in combination, to increase chances for successes. 

Technology's Essence


The ligand-receptor network consisting of NRG1, and its tyrosine kinase receptors ERBB4, ERBB3 and ERBB2, plays critical roles during heart development.
In a multidisciplinary study, headed by prof. Eldad Tzahor from the Weizmann institute of Science, ERBB2 was shown to be necessary and limiting for NRG1-induced CM proliferation in the neonate.
Inspired by this finding, the team examined the possibility to use ERBB2 as a target for induced cell proliferation and regeneration in adult hearts. Using loss- and gain-of-function genetic experiments in mice, they reveal that NRG1/ERBB2 signalling is both essential for CM proliferation and heart integrity in the neonatal period, and sufficient to prolong the postnatal proliferative and regenerative windows.
Regeneration was shown to be a result of increased CM dedifferentiation and proliferation accompanied by neovascularization and followed by redifferentiation, tissue replacement with reduced scar formation and restoration of function.
Thus, these finding highlight ERBB2 as a strong target for heart regeneration treatments as well as its downstream effectors.

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  • Prof. Eldad Tzahor
1671
A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined...

A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined conditions required for derivation and long term maintenance of such cells, without genetic modification.
Human naive pluripotent cells can be robustly derived either from already established conventional hESC lines, through iPSC reprogramming of somatic cells, or directly from ICM of human blastocysts. The new human pluripotent state was isolated and characterized; it can open up new avenues for patient specific disease relevant research and the study of early human development.

Applications


  • Reprogramming kits - Somatic cells to iPSC at near 100% efficiency (7days), iPSC to fully naive state.

Advantages


  • Deterministic iPSC reprogramming with no genetic modification required.
  • Stable pluripotency, with low propensity for differentiation
  • Reagents available off-the-shelf.

Technology's Essence


Hallmark features of rodent naive pluripotency include driving Oct4expression by its distal enhancer, retaining a pre-inactivation state of X chromosome in female pluripotent cell lines amongst others. Naive mouse ESCs epigenetically drift towards a primed pluripotent state; while human embryonic stem cells (hESCs) share several molecular features with naive mESCs (e.g. expression of NANOG, PRDM14 and KLF4 naive pluripotency promoting factors), they also share a variety of epigenetic properties with primed murine Epiblast stem cells (mEpiSCs). These observations have raised the question of whether conventioal human ESCs and induced pluripotent stem cells (iPSCs) can be epigenetically reprogrammed into a different pluripotent state, extensively similar with rodent na?ve pluripotency. Researchers at the Weizmann Institute discovered that supplementation of certain chemically defined conditions, synergistically facilitates the isolation and maintenance of pluripotent stem cells that retain growth characteristics, molecular circuits, a chromatin landscape, and signaling pathway dependence that are highly similar to naive mESCs, and drastically distinct from conventional hESCs.

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  • Dr. Jacob (Yaqub) Hanna
1717
Converting two low-energy photons into a single higher-energy photon is of significant importance in many fields. In medical imaging, photon up-conversion is used for imaging scattered specimens, while in photovoltaic devices it could be used to harvest photons with energies lower than the bandgap of...

Converting two low-energy photons into a single higher-energy photon is of significant importance in many fields. In medical imaging, photon up-conversion is used for imaging scattered specimens, while in photovoltaic devices it could be used to harvest photons with energies lower than the bandgap of the absorber.
Currently available systems, based on rare-earth-doped dielectrics, and organic materials are limited in both tunability and absorption cross-section. In fact, no known up-conversion systems operate on photons in the 1000-1500 nm range.
Stable inorganic nanocrystalline up-conversion systems designed at the Weizmann Institute of Science provide broad tunability of both the absorption edge and the luminescence color. These materials have the potential to be utilized in applications such as high-energy photon sources, photovoltaics and IR detection.

Applications


  • Easy to manufacture

  • Robust systems

  • Operation at room temperature


Advantages


  • Photon sources

  • Photovoltaics

  • IR detectors


Technology's Essence


The new up-conversion systems are based on a novel design comprising a compound semiconductor nanocrystal, which incorporates two quantum dots with different bandgaps separated by a tunneling barrier. The expected up-conversion mechanism occurs by the sequential absorption of two photons. The first photon excites an electron–hole pair by interband absorption in the lower-energy core, resulting in a confined hole and a relatively delocalized electron. The second absorbed photon leads to further excitation of the hole, allowing it to cross the barrier layer. This, in turn, is followed by radiative recombination with the delocalized electron.

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  • Prof. Dan Oron
1765
A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron.  Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns....

A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron. 
Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns. These techniques utilize radiation in the X-ray regime to image non-periodic objects in sizes that prohibit the use of larger wavelengths. However, retrieving the phase information of the diffraction pattern is not a trivial task, as current methods are divided based on a tradeoff between experimental complexity and computational reconstruction efficiency.
The method described here is suitable for use with existing lensless imaging techniques to provide direct, robust and efficient phase data while requiring reduced computational and experimental complexity. This method, demonstrated in a laboratory setup on 2D objects, is also applicable in 1D. It can be applied to various phase retrieval applications such as coherent diffractive imaging and ultrashort pulse reconstruction

Applications


  • Phase microscopy
  • Signal processing
  • Holography
  • X-ray imaging

Advantages


  • A Generic solution to the phase retrieval problem
  • Non-iterative approach
  • An efficient and noise robust tool

Technology's Essence


The method is based on the fact that the Fourier transform of the diffraction intensity measurement is the autocorrelation of the object. The autocorrelation and cross-correlations of two sufficiently separated objects are spatially distinct. Based on this, the method consists of three main steps: (a) The sum of the objects’ autocorrelations, as well as their cross-correlation, are reconstructed from the Fourier transform of the measured diffraction pattern. (b) The individual objects’ autocorrelations are reconstructed from their sum and the cross-correlation. (c) Using the two intensities and the interference cross term, double-blind Fourier holograph is applied to recover the phase by solving a set of linear equations.

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  • Prof. Dan Oron
1673
CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical...

CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical importance in patients with chronic obstructive pulmonary disease (COPD), trauma, burn wounds, sepsis, or in patients requiring ventilation. The infections are currently treated with antibiotics, which rapidly become inefficient as resistant bacteria strains arise. The present technology suggests a novel therapeutic approach for the prevention and treatment of bacterial lung infection in susceptible populations, especially CF patients

Applications


  • Alternative treatment for bacterial lung infections.
  • A prophylaxis for patients susceptible to bacterial lung infections

Advantages


  • A novel therapeutic approach to prevent or cure bacterial lung infection.
  • The new therapy is based on reinforcement of the physiological innate immunity rather than on antibiotics.
  • The new therapy can be easily administered, via inhalation.
  • FTY720, a SPH analog, is already in clinical use for treating multiple sclerosis.

Technology's Essence


Sphingosine (SPH), a natural bactericidal agent which acts as a part of the human innate immune system in the skin, was found to be an effective treatment and prophylaxis for bacterial lung infections in cystic fibrosis (CF) mice. The new technology is based on the discovery that both CF human patients and CF mice display reduced rates of SPH in the airways. Moreover, normalizing SPH levels by inhalation prevents or cures the infections in CF mice, thus rendering SPH and its analogs a potent therapeutic agent for CF patients, an alternative to antibiotics.

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  • Prof. Anthony H. Futerman
1730
Production of carbon nanotube based transistors through a process comprised of identification, selection, and placement of pristine carbon nanotubes in conjunction with standard electrical circuitry.Semiconductor devices are vital to everyday life, however conventional semiconducting materials are...

Production of carbon nanotube based transistors through a process comprised of identification, selection, and placement of pristine carbon nanotubes in conjunction with standard electrical circuitry.
Semiconductor devices are vital to everyday life, however conventional semiconducting materials are quickly approaching their limitations. As devices transition from the microscale to the nanoscale, new techniques for their assembly and testing of their properties must be created. Controllable nanofabrication methods are of increasing importance across a wide field of electronics in everything from energy efficient LEDs in flat-screen monitors to transistors for ultra-powerful computers. Our process presents a novel method for producing high quality nanoscale carbon nanotube based transistors. These methods will be of the utmost importance in the forthcoming nano-revolution.

Applications


  • Produce flawless carbon nanotubes
  • Identify, select, and position nanotubes with precision
  • Room temperature operation
  • High sensitivity
  • High resolution

Advantages


  • Single electron transistor (SET) nanoscale imaging
  • Novel nano-electromechanical devices

Technology's Essence


The principle behind this technology is two-fold: 1) Synthesis and selection method of flawless carbon nanotubes, and 2) their combination with nanoscale electric circuitry to form fully controlled composite nanoscale electronic device.
Selection of the carbon nanotube(s) is assisted by a scanning probe microscope (SPM). A composite electronic device is assembled from two separated chips; a nanotube chip where nanotubes are grown over wide trenches, and a standard circuit chip with electrode contacts surrounding the gates to be measured. The nano-assembly is achieved by inserting an SPM cantilever into a trench on the nanotube chip and placing the circuit chip over a suitable nanotube. Once in place, the nanotube is cut locally by passing a strong current between the electrode contacts, and the composite chip is formed.
This composite electronic device can be used to map electronic potentials with high resolution of 100 nm, high sensitivity of 1microV/Hz1/2, at frequencies of 100 MHz and more and all this at room temperature.

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  • Prof. Shahal Ilani
1780
A method based on Fast Neutron Resonance Transmission (FNRT) radiography that enables determining weight percentages of oil and water in thick, intact cores taken from subterranean or underwater geological formations. As part of geological exploitation to find oil and water, cores are extracted and...

A method based on Fast Neutron Resonance Transmission (FNRT) radiography that enables determining weight percentages of oil and water in thick, intact cores taken from subterranean or underwater geological formations. As part of geological exploitation to find oil and water, cores are extracted and tested to determine oil/water content.
This new method allows determining such content rapidly, in non- destructive, specific and quantities analysis of the cores.

Applications


  • Determining the identity and proportions of substances of oil and water content and their distribution in inspected cores

Advantages


  • A non-destructive method which enables to determine the fluid content along the entire length of an intact core or aggregate of cores within their protective sleeves.
  • More comprehensive information and considerable saving of analysis time compared to conventional sampling methods.
    Suitable for all types of rocks including tight-shale rocks.
  • This method enables to measure the weight fraction of oil and water in the core regardless of the core shape, thickness or distribution.
  • The fluid weight fractions in the samples are determined independently, thus the ratio of oil-to-rock weight-ratio is independent of the water content.
  • Due to high penetration of fast neutrons, the method is suitable for screening intact thick rock cores (10-15 cm), for which alternative probes, such as X-rays or slow neutrons suffer limited penetration.

Technology's Essence


In order to map the oil and water content and their distribution, an aggregate of intact cores within their protective sleeves is positioned on a moving conveyor belt and scanned by a broad- energy, fast- neutron beam. The neutrons are detected by a spectroscopic fast neutron imaging detector. The map of neutron-transmission spectra in each pixel provides information of oil/water content and distribution in such cores. 

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  • Prof. Amos Breskin
1684
Gaseous energy sources such as hydrogen and natural gas (predominantly methane) encompass an intrinsic transport problem because of their volatility and flammability. Adsorption of the gas on a solid material (such as MOF) facilitates safe, light and economical transport of the gas. This is especially...

Gaseous energy sources such as hydrogen and natural gas (predominantly methane) encompass an intrinsic transport problem because of their volatility and flammability. Adsorption of the gas on a solid material (such as MOF) facilitates safe, light and economical transport of the gas. This is especially significant in the huge natural gas (NG) market where solutions are required for storage and transport of the gas whether from NG reservoirs in high pressure giant tanks or as a compact low pressure NG tank for small vehicles and other NG powered devices.
The invention involves a new method for the formation of uniform metal organic frameworks (MOFs) at quantitative yields and in a controlled manner.
These MOFs can be tailored to adsorb specific gases for low pressure - high volume storage and transport applications.

Applications


  • Low pressure – high volume gas storage and transportation
  • Safe storage of toxic or otherwise dangerous gases
  • Low energy solid phase gas separation and purification
  • Production of MOF-based catalysts

Advantages


  • Uniform crystallite morphology
  • A quantitative process
  • Ability to design and control product structure
  • Control of pore size
  • Single step process
  • No additives

Technology's Essence


The invention comprises a new solvothermal synthetic procedure in which specific metal ions are selected to react with specific organic ligands to form uniform sub-microstructured MOFs with a narrow size distribution and without the need for a modulator to define the crystal morphology.
Controlling the selected reagents as well as the specific reaction conditions influences the resulting crystallites formed and enables a fine selection of the desired structure.
MOFs prepared this way have exceptional uniformity profiles of size and shape and can be tailored to selectively adsorb specific gases for low pressure - high volume storage and transport applications.

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  • Prof. Milko E. Van der Boom
1749
Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity. Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is...

Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity.
Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is highly diffusive and buoyant. Currently, hydrogen is stored physically as a gas, requiring high-pressure tanks, or in liquid form at cryogenic temperatures, both methods require high energy input. Proposed chemical storage systems are based on relatively expensive materials, suffer from poor regeneration after hydrogen release and require elevated temperatures and pressures.
The presented technology utilizes inexpensive and abundant organic compounds that generate hydrogen gas during a chemical transformation. Hydrogen release and the regeneration of the original compound are performed in mild conditions using the same catalyst. This system is a promising candidate to be the basis of compact and cost-effective chemical hydrogen storage platforms.

Applications


  • High potential hydrogen storage capacity (6.6 wt%)
  • Inexpensive and readily available hydrogen carriers (aminoalcohols)
  • Relatively mild release and regeneration conditions

  • Advantages


    • Hydrogen-fueled systems, including fuel cells
    • High capacity hydrogen storage systems

    Technology's Essence


    The technology is based on aminoalcohols that are catalytically converted to cyclic dipeptides, while forming hydrogen gas, using a ruthenium pincer catalyst. Peptide hydrogenation, using the same catalyst, regenerates the aminoalcohol. The same method can be applied with diaminoalkanes and alcohols as well.
    The reaction requires a relatively low organic solvent volume, a catalytic amount of base (KOtBu) for the in situ generation of the active catalyst and mild reaction conditions in terms of hydrogen pressure (50 bar) and temperature (~100 oC). Repetitive cycles of the dehydrogenation-hydrogenation reactions can be performed without adding new catalyst, while maintaining high percentages of aminoalcohol conversion.

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    • Prof. David Milstein
    1800
    A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses. The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt...

    A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses.

    The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt stimulations. This may allow TMS-EEG to be used as a diagnostic tool for various neurologic and psychiatric conditions.

    However, large electric artifacts are induced in the EEG by the TMS, which are unrelated to brain activity and obscure crucial stages of the brain's response. These artifacts are orders of magnitude larger than the physiological brain activity, and persist from a few to hundreds of milliseconds. However, no generally accepted algorithm is available that can remove the artifacts without unintentionally and significally altering physiological information.

    The software designed according to the model along with a friendly GUI is a powerful tool for the TMS-EEG field. The software has tested and proven to be effective on real datasets measured on psychiatric patients.

    Applications


    • TMS triggered EEG diagnostics

    Advantages


    • Easy to use software with a GUI
    • Exposes the full EEG from the brain

    Technology's Essence


    The new software tool is based on the observation that, contrary to expectation, the decay of the electrode voltage after the TMS pulse is a power law in time rather than an exponential. A model based on two dimensional diffusion of the accumulated charge from the high electric
    fields of the TMS in the skin was built. This model reproduces the artifact precisely, including the many perplexing artifact shapes that are seen on the different electrodes. Artifact removal software based on this model exposes the full EEG from the brain, as validated by continuously reconstructing 50Hz signals that are the same magnitude as the brain signals.

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    • Prof. Elisha Moses
    1710
    Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways...

    Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways.
    Anti-microbial peptides (AMPs) possess promising anti-inflammatory activities, however, are commonly toxic.
    In a series of newly synthesized peptides, the outlined invention provides a method to modify naturally occurring AMPs to possess both potent therapeutic anti-inflammatory activity and minimal toxicity in-vitro and in-vivo.
    The resulting series of peptides were shown to remarkably inhibit severe allergic reaction as well.

    Applications


    • Novel Therapy for sepsis and severe allergic reactions

    Advantages


    • Very potent anti-inflammatory and anti-allergenic agents
    • Non-toxic
    • Targeted against the underlying cause of both indications, which is an improper and uncontrolled immune response
    • Diversity – elucidating the parameters that control efficiency and toxicity allows to modify the basic formula to optimally fit different systems

    Technology's Essence


    With natural AMPs properties in mind, Prof. Shai and his team characterized the key modifications that underline anti-inflammatory activity and toxicity. A series of peptides with variable degrees of hydrophobicity, length, charge, position of charge and amino acid chirality were tested for their LPS neutralizing activity.
    It was found that ~20mer peptides under the formula Kn(AL)mKn (wherein n et each occurrence is independently 0-2, and m is 6-9) demonstrate anti-inflammatory activities at nanomolar concentrations as evident by inhibition of TNF? secretion from macrophages, following  LPS induction. Furthermore, a single dose of an exemplary peptide was able to inhibit septic shock in mice induced by purified LPS or by whole heat-killed E.coli.
    In contrast to previous attempts, which focused on increasing hydrophobicity, the core of the present invention is the designation of an optimal hydrophobicity that is necessary for high activity and low toxicity. Additional important features for LPS neutralizing were found to be ?-helical structure and strong oligomerization ability.
    Surprisingly, the present peptides were shown to contain highly potent anti-allergenic activity as well. In-vitro inhibition of Fc?RI-mediated degranulation was recapitulated in-vivo  

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    • Prof. Zelig Eshhar
    1751
    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets. The present...

    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets.
    The present discovery elucidates the pathway by which argininosuccinate synthase (ASS1) down-regulation confer cancer progression. It shows that decreased activity of ASS1 in cancers supports proliferation by linking excess aspartate to pyrimidines synthesis. Importantly, these studies highlight Citrin (a mitochondrial aspartate transporter) inhibition as a potential method to decrease aspartate levels and selectively target this metabolic pathway in ASS1 depleted cancers.

    Applications


    • Targeted Treatment for ASS1 depleted cancers.

    Advantages


    • Targeted therapy, against a well defined pathway, increases the prospects for success.
    • Selective – targeting cancer metabolic dependency minimizes the chances for healthy cells damage that lead to side effects.

    Technology's Essence


    Cancer cells hijack and remodel existing metabolic pathways for their benefit in what is termed the Warburg effect. Researchers from Dr. Ayelet Erez's lab, at the Weizmann institute of Science, have delineated the metabolic benefit(s) conferred by loss of ASS1 to cancers. In agreement with previous experience, they found that ASS1 deficiency has an additional arginine- independent effect that is directly related to its substrate, aspartate.
    By focusing on the relevant physiological and pathological model systems, it was found that ASS1 deficiency-mediated increase in aspartate levels lead to excessive proliferation through pyrimidine synthesis. The link between the two is provided by CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, dihydroorotase complex) and the mTOR signaling pathway.
    Importantly, the present inventors have found that blocking Citrin, the mitochondrial aspartate transporter, rescues cell proliferation by reducing aspartate levels. Citrin may thus serve as a strong candidate for targeted therapy of ASS1 depleted cancers.   
    Supporting this model, retrospective survival analysis of several cancers reveal that cancers with both decreased ASS1 expression and high Citrin levels have a trend for significantly worse prognosis.

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    • Dr. Ayelet Erez

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