Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Haim Zakut

Hermona Soreq

Moshe Shani

Fritz Eckstein

The present invention relates to novel alternative forms of human acetylcholinesterase (AChE) and nucleotide sequences encoding the same. The genes encoding the novel forms of human AChE have been identified in various malignant tumor cells. In a further aspect, the invention relates to a transgenic animal assay system for evaluating efficacy of drugs against cholinergic proteins, prior to or in the course of therapeutic treatment. Transgenic animals, preferably developing tadpole ofor mice which express human AChE, are used. The transgenic animal assay system is also useful for evaluating the toxicity of substances which potentially block human AChE (e.g. organophosphorous compounds).

Transgenic non-human mammals producing a cholinesterase in their milk

A method of screening for a genetic predisposition to anticholinesterase exposure. The method includes the steps of obtaining a peripheral blood sample, and then analysing serum from the blood sample for BuChE levels and inhibitor-susceptibilities. The DNA of peripheral white blood cells from the blood sample is also screened for the presence of BuChE alleles thereby identifying patients who have a genetic predisposition to anticholinesterase exposure.

Method of screening for genetic predisposition to anticholinesterase therapy

The present invention provides a transgenic animal assay system which provides a model system for testing for, and treatment of, cholinergic deficits and imbalances in mammals such as cognitive functioning in Alzheimer's patients, certain types of retinal photoreceptor degeneration, hematopoietic disorders, and screening for and susceptibility to anti-cholinesterase compounds. The transgenic animals and progeny thereof are transformed with a recombinant expression vector of the present invention. The recombinant expression vector comprises a DNA sequence encoding a heterologous cholinesterase (ChE) enzyme and promoter.

Transgenic animal assay system for anti-cholinesterase substances

The present invention relates to novel alternative forms of human acetylcholinesterase (AChE) and nucleotide sequences encoding the same. The genes encoding the novel forms of human AChE have been identified in various malignant tumor cells. In a further aspect, the invention relates to a transgenic animal assay system for evaluating efficacy of drugs against cholinergic proteins, prior to or in the course of therapeutic treatment. Transgenic animals, preferably developing tadpole of Xenopus or mice which express human AChE, are used. The transgenic animal assay system is also useful for evaluating the toxicity of substances which potentially block human AChE (e.g. organophosphorous compounds).

Transgenic non-human animal assay system for anti-cholinesterase

Synthetic antisense oligodeoxynucleotides and pharmaceutical

A method of screening for a genetic predisposition to anticholinesterase exposure. The method includes the steps of obtaining a peripheral blood sample, and then analysing serum from the blood sample for BuChE levels and inhibitor-susceptibilites. The DNA of peripheral white blood cells from the blood sample is also screened for the presence of BuChE alleles thereby identifying patients who have a genetic predisposition to anticholinesterase exposure.

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Savyon, Israel

Haim Zakut