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1451
A monoclonal antibody against GluR3B, a peptide found in epilepsy patients, and especially in patients suffering from intractable, resistant forms of the disease, could be used in diagnosis kits as well as in drug development for this form of "autoimmune epilepsy".

A monoclonal antibody against GluR3B, a peptide found in epilepsy patients, and especially in patients suffering from intractable, resistant forms of the disease, could be used in diagnosis kits as well as in drug development for this form of "autoimmune epilepsy".

Applications


1. Producing a new kit for epilepsy patients, able to detect GluR3b Ab's and thus GluR3-mediated neuropathology
The anti GluR3B monoclonal Ab could be used for developing a new diagnostic kit to detect neuropathogenic human anti-GluR3B in serum and CSF of patients with epilepsy. The patient's GluR3B Ab's would compete and displace the GluR3B mAb's of its ligand: the GluR3B peptide. The presence of GluR3B Ab's in a patient, would indicate that autoimmunity against GluR3 may underlie the patient's neuropathology and a) would suggest the initiation of an immune-based therapy b) prevent useless and dangerous brain surgery c) prevent non-effective medication.

2. Drug design for GluR3-mediated neuropathology
The unique GluR3B monoclonal antibody could be used to screen a potential drug for 'Autoimmune Epilepsy'. The GluR3B monoclonal antibody could be used to screen for a molecule (i.e. Anti-idiotypic antibodies) that would block the GluR3 autoantibodies and their detrimental neuropathological effects.

3. Research tool for a kaleidoscope of purposes, including:

  • Detection of the GluR3 glutamate receptor subtype on various target cells.
  • Studies of the properties of the Glutamate/AMPA receptor subtype 3.
  • Studies of the Glutamate-liked agonist activity of the GluR3B monoclonal antibody, and of the GluR3 receptor ion channel gating properties.
  • Production of an animal model of 'Autoimmune Epilepsy'.
  • Studies of neuronal death caused by binding of the GluR3 autoantibody to glutamate/AMPA receptors.
  • Studies of behavioral impairments caused by binding of the GluR3 autoantibody to glutamate/AMPA receptors.

  • Technology's Essence


    Scientists from the Weizmann Institute of Science have discovered a unique anti-GluR3B monoclonal antibody Glu149/29/61.

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    • Prof. Vivian I. Teichberg
    • Prof. Vivian I. Teichberg
    1033
    A novel diagnostic test to identify individuals with increased risk of lung cancer. Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the...

    A novel diagnostic test to identify individuals with increased risk of lung cancer.

    Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the National Lung Cancer Trial (NLST) showed that early detection of lung cancer by low-dose CT reduces mortality by at least 20%. Despite recommendations for low-dose CT screening for heavy smokers fulfilling the NLST criteria, compliance is low. In addition, 80 million smokers and ex-smokers in the US who do not fulfil NLST risk criteria have no recommended solution.

    The MyRepair test fulfils this unmet medical need by providing a quantitative prediction of lung cancer risk using a simple blood test. The test is based on a personalized measurement of the patient’s DNA repair capacity, a mechanism which is highly connected to the onset of cancer. Therefore, the MyRepair technology can potentially increase early detection of lung cancer and thus save lives.

     

    Applications


    A novel diagnostic test to identify individuals with increased risk of lung cancer


    Advantages


    ·         Simplicity – MyRepair is based on a simple, cost-effective blood test.

    ·         Accessibility – Compared to low-dose CT which requires specific equipment, the MyRepair test can be easily integrated in general diagnostic labs and therefore may be more accessible to a larger portion of the population.

    ·         Additional applications – Since the test is based on measuring personalized DNA repair mechanism, it can be adopted in the future for the diagnosis of additional cancer types and DNA repair related diseases.


    Technology's Essence


    Based on the strong and well documented connection between impaired capacity for DNA repair and onset of cancer, the Livneh lab invented the MyRepair Test, a method for predicting lung cancer risk, based on measuring activity of 3 DNA repair enzymes.

    Combining enzyme activities with experimental risk estimates generated MyRepair Score, which measures personalized DNA repair capacity of tested subjects.

    An epidemiological/clinical study performed in Israel, further validated in an independent UK study, demonstrated that lung cancer patients have lower MyRepair Score than healthy people. In addition, subjects who test MyRepair-positive have an 85-fold higher risk to develop lung cancer compared to the general population.

    Low MyRepair Score is a risk factor independent of smoking, and of comparable magnitude, indicating that it can be a prognostic tool for smokers, ex-smokers, and non-smokers.

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    • Prof. Zvi Livneh
    1518
    Improved immunotherapy for breast cancer. Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of...

    Improved immunotherapy for breast cancer.

    Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of therapeutic mAbs and the evolution of patient resistance call for improvements. Furthermore, the response to the clinically approved monotherapy of Herceptin (a humanized mAb directed against ErbB-2), is relatively low (~15%) and short lived (median duration, 9 months). Therefore, there is a need to improve the therapeutic treatment against this receptor. The present technology enhances the therapeutic activity of anti-ErB-2 receptor antibodies, by combining two or more epitope-distinct antibodies.

    Applications


    • Improved treatment of ErbB-2-overexpressing tumors (e.g. in breast and ovary cancers).


    Advantages


    • May enhance patient response and delay acquisition of resistance.
    • Enhancement of therapeutic efficacy and synergy with chemotherapy.

    Technology's Essence


    Optimal selection of mAbs for cancer immunotherapy may improve its therapeutic potential. The outlined technology addresses an emerging strategy, which enhances the therapeutic activity of anti-receptor antibodies by combining two mAbs engaging distinct epitopes. It was demonstrated that pairs of anti-ErbB-2 mAbs better inhibit ErbB-2-overexpressing tumors than the respective individual mAbs, both in vitro and in vivo.

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    • Prof. Yosef Yarden
    1270
    Monoclonal antibodies to IgE Description: Rat monoclonal anti-IgE antibodies that was generated by fusion of plasmacytoma (84.1C) or myeloma (EM953) cells with splenocytes of rat immunized with purified murine IgE mAb. The antibodies react with various IgE mAb of different specificities and not with...

    Monoclonal antibodies to IgE

    Description: Rat monoclonal anti-IgE antibodies that was generated by fusion of plasmacytoma (84.1C) or myeloma (EM953) cells with splenocytes of rat immunized with purified murine IgE mAb. The antibodies react with various IgE mAb of different specificities and not with immunoglobulins of other classes, and recognize an epitope on the murine Fc epsilon region.

    Were shown to block IgE-Fc?R interactions and inhibit passive cutaneous anaphylaxis. 

    Clone 84.1c recognizes a site on IgE, which is identical or very close to the Fc?R binding site. May be used for detection and manipulation of the IgE response in mice.

    Reference:  Schwarzbaum S, Nissim A, Alkalay I, Ghozi MC, Schindler DG, Bergman Y, Eshhar Z. 1989. Mapping of murine IgE epitopes involved in IgE-Fc epsilon receptor interactions. Eur J Immunol 19(6):1015-23.

     

    M182, M185, M186

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    • Prof. Zelig Eshhar
    1668
    Despite progress in early detection and treatment, breast cancer remains a leading cause of cancer-related death in women. For example, in 2012 alone, 41,150 women in the United States died from breast cancer. Targeted therapies, which are based on oncogenic genetic abnormalities, are commonly used to...

    Despite progress in early detection and treatment, breast cancer remains a leading cause of cancer-related death in women. For example, in 2012 alone, 41,150 women in the United States died from breast cancer.

    Targeted therapies, which are based on oncogenic genetic abnormalities, are commonly used to treat subgroups of breast cancer patients. Although these treatments show promising results, they are limited to only a subgroup of patients (for example, amplification of HER2 occurs in about 15% of breast cancers) and there is an unmet need for the identification of druggable targets with a major oncogenic role in breast cancer development.

    The present invention relates to the identification of SYNJ2 as a novel target for breast cancer treatment. SYNJ2 expression is enhanced in a sub-population of breast cancer patients and its catalytic activity was shown to promoted cell migration and invasion. Furthermore, screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration, suggesting that SYNJ2 is a potential target for cancer treatment.

    Applications


     


    Advantages


    • Novel identification of SYNJ2 as a genetically aberrant and potentially druggable driver of tumor progression.
    • Specificity – the discovered SYNJ2 inhibitors do not inhibit SYNJ1 which plays additional roles in the nervous system.
    • Potential therapeutic effect – Inhibition of SYNJ2 in several cancer models blocks tumor progression and invasion.


    Technology's Essence


    SYNJ2 abundance is increased in breast tumors and it is correlated with poor prognosis and aggressive subtypes of breast cancer. Furthermore, growth factors involved in breast cancer metastasis can increase SYNJ2 expression in association with increased cell invasion.

    SYNJ2 is localized to cellular protrusions involved in migration and matrix invasion and its phosphatase activity enhances tumor growth and metastasis in mice. Unlike wild-type SYNJ2, reexpression of a catalytic inactive mutant failed to restore invasiveness of cancer cells, indicating that the catalytic activity of SYNJ2 is essential for motility.

    Using a high-throughput screening platform for the measurement of SYNJ2 activity, four specific SYNJ2 inhibitors were discovered. All of the four inhibitors were selective to SYNJ2 and didn’t have an effect on its brain-enriched kin, SYNJ1. In addition, all four compounds attenuated cellular invasion, suggesting that specific SYNJ2 inhibitors can be developed as potential drugs for cancer therapy.

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    • Prof. Yosef Yarden
    • Prof. Yosef Yarden
    1655
    Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and...

    Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and promote a number of pathological conditions. Therefore the elimination of senescent cells is desired in order to prevent tumor- and inflammation- related pathologies and also to inhibit tissue ageing.
    Today, our understanding of the mechanisms regulating the viability of senescent cells is limited. It has been suggested that senescent cells are resistant to apoptosis. Therefore, senescent cells elimination may be achieved by modifying the resistance to apoptosis of these cells.
    Here the researches demonstrate the first feasible therapeutic approach that leads to eradication of senescent cells. Combination of direct induction of apoptosis in senescent cells with induction of cell death by pro-inflammatory repose induce by p21 knockdown will lead to reduction of viable senescent cells.

    Applications


    • A therapeutic impact on inflammatory and fibrotic disease
    • Therapy for age-related disease such as type 2 diabetes, Alzheimer’s disease, Atherosclerosis, cataracts, Chronic obstructive pulmonary disease (COPD), and Osteoporosis

    Advantages


    • Effective elimination of senescent cells- removal of senescent cells can prevent or delay tissue dysfunction and extend health span
    • Does not damage normal cells even at high concentrations

    Technology's Essence


    Researches demonstrated that the anti-apoptotic proteins Bcl-xL and Bcl-w level were elevated in senescence cells of both human and mouse origin. A subsequent study, in which Bcl-xL and Bcl-w were knocked down by siRNA, revealed that a combined knock down of Bcl-xL and Bcl-w had synergic effect, resulting in reduction of 50% in cell viability. Thus the increased level of anti-apoptotic proteins Bcl-xL and Bcl-w may account for the apoptotic resistance of senescent cells. p21 knockdown induced pro-inflammatory response and cell death in senescent cells.
    Overall, the researchers show that combined inhibition of the anti-apoptotic proteins Bcl-xL and Bcl-w allows specific elimination of senescent cells and might be used to treat diseases where senescent cells are present. The researchers also found that the same effect might be achieved by reducing the expression of p21 in senescent cells. Integrating both approaches propose a more effective therapy.

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    • Ph.D. Valery Krizhanovsky
    1498
    MicroRNAs as potential biomarkers for ALS.Amyotrophic Lateral Sclerosis (ALS) is a devastating disease that progressively destroys motor neurons in the brain and the spinal cord, eventually causing paralysis and death. Currently, there are approximately 25,000 patients with ALS in the USA, with a...

    MicroRNAs as potential biomarkers for ALS.
    Amyotrophic Lateral Sclerosis (ALS) is a devastating disease that progressively destroys motor neurons in the brain and the spinal cord, eventually causing paralysis and death. Currently, there are approximately 25,000 patients with ALS in the USA, with a median age of onset of 55 years. Approximately 5–10% of patients with ALS have a family history, and these patients most frequently inherit the disease in an autosomal dominant manner. Family-based linkage studies have led to the identification of several genes for familial ALS. However these findings only explain a small fraction of all ALS cases. The majority of ALS cases have no obvious family history and are referred to as sporadic ALS. At present, there is no effective therapy for the disease and patients usually die within 2-5 years after the onset of symptoms. Thus, there is an urgent need for biomarkers that could substantially aid early diagnosis of ALS and will help in designing decisive clinical trials of new drugs. The present technology provides specific microRNAs that can serve as potential biomarkers for ALS.

    Applications


    • Unique patterns of microRNA expression profile in the cerebrospinal fluid of ALS patients could be useful as molecular biomarkers for disease diagnosis and eventually prediction of therapeutic responses.
    • The suggested ALS biomarkers may be employed in drug development studies.

     


    Advantages


    •  MicroRNAs can be precisely quantified using qRT-PCR that provides exceptionally high sensitivity and specificity of detection.
    • The small size of microRNAs offers a unique advantage since they are more stable and less prone to enzymatic degradation, and are therefore amenable to an accurate assessment of their expression levels.

    Technology's Essence


    MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression in a posttranscriptional fashion and contribute to a wide variety of biological processes. miRNAs play important roles in the development of the central nervous system and their involvement in neurodegenerative diseases such as Parkinson's disease and Alzheimer’s disease has been recently established. The outlined technology describes specific miRNAs that are enriched in motor neurons and are significantly downregulated in mouse models of hereditary motor neuron disease (SOD1G93A and SMN1). These miRNAs may serve as putative biomarkers for motor neuron diseases such as ALS by measurement of their expression levels in cerebrospinal fluid samples collected from affected individuals.

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    • Dr. Eran Hornstein
    1698
    GD is an inherited metabolic disorder, affecting about 1 in 20,000 births. GD is divided into three clinical subtypes: type 1 is the most common and is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. Types 2 and 3, also called neuronopathic GD (...

    GD is an inherited metabolic disorder, affecting about 1 in 20,000 births. GD is divided into three clinical subtypes: type 1 is the most common and is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. Types 2 and 3, also called neuronopathic GD (nGD), affect 4% of GD patients and additionally include neurological symptoms. Type 1 patients can have a normal life expectancy if treated whereas type 2/3 patients do not survive to reach adulthood. Moreover, GD carriers, approximately 1% of the population, are in a major risk of developing Parkinson’s disease. Current therapies suffer from severe drawbacks in the treatment of type 1 GD and no therapy exists that effectively treat nGD. The present technology offers a novel therapeutic target for the treatment of Gaucher's disease (GD) which addresses also the neurological symptoms.

    Applications


    • Alternative treatment for type 1 GD
    • First line therapy for nGD

    Advantages


    • A novel therapy for nGD which has no treatment for the present.
    • A novel therapeutic approach for GD type 1, via a previously unknown molecular mechanism.
    • Allows the development of an orally administered treatment, far more convenient for the patients than the existing treatments.
    • Reduced costs compared to the existing therapies of ERP or BMT

    Technology's Essence


    The proposed technology is based on the discovery that RIP3 is a key player in the manifestation of GD and that inhibiting RIP3 activity is effectively ameliorating the symptoms of GD not only in the less severe type 1 but also in the neuropathic form of the disease, types 2 and 3. nGD is associated with a massive neuronal loss and elevated RIP3 levels. Inhibition of RIP3 in a mouse model of nGD resulted in a dramatic attenuation of disease signs: drastic extension of life span, no weight loss, improvements in motor coordination, reduced neuroinflammation and improved liver and spleen injuries.

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    • Prof. Anthony H. Futerman

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