Abstract: Briefly stated, the invention includes a method of making a transgenic plant that is capable of expressing a physiologically active human acetylcholinesterase, comprising the steps of introducing into at least one plant cell a polynucleotide that encodes a human acetylcholinesterase, and regenerating from the plant cell a transgenic plant that is capable of expressing a physiologically active human acetylcholinesterase in at least one tissue type of the transgenic plant.

Abstract: The invention provides a transgenic rodent whose genome comprises a mutant hAPP transgene and an hAChE transgene. Methods and materials for making such transgenic rodents, and using them to identify agents that affect the progression of Alzheimer's disease are also provided.

Abstract: The invention relates to an antisense oligonucleotide targeted to the coding region of the human acetylcholinesterase (AChE), which selectively suppresses the AChE-R isoform of the enzyme. The antisense oligonucleotide is intended for use in the treatment and/or prevention of neuromuscular disorders, preferably myasthenia gravis. In addition, it can penetrate the blood-brain barrier (BBB) and destroy AChE-R within central nervous system neurons, while also serving as a carrier to transport molecules across the BBB.

Abstract: The invention relates to a cell growth and/or differentiation regulatory peptide comprising a sequence of about 9 to about 150 amino acids derived from acetylcholinesterase amino acid sequence, preferably from the C-terminal region of acetylcholinesterase. The invention also relates to pharmaceutical compositions comprising the peptides, particularly for use in promoting survival of stem cells, promoting differentiation of stem cells, promoting growth of stem cells and/or promoting the growth-enhancing effect of a growth factor on stem cells, alone, or in combination with other growth factors. Of particular interest is the use of the peptides in the treatment of thrombocytopenia, post-irradiation conditions, post-chemotherapy conditions, or conditions following massive blood loss and promotion of neural progenitors in use for cell therapies aimed at restoring neural functions in diseased individuals.

Abstract: The invention provides methods and pharmaceutical compositions thereof for treating injury to the central nervous system (CNS). The method includes administering to the CNS of a patient suffering from such an injury a therapeutically effective amount of an inhibitor of acetylcholinesterase (AChE) production immediately following the injury. The methods use as the inhibitor a synthetic nuclease resistant antisense oligonucleotide or ribozyme that is directed against an accessible domain of the AChE mRNA brain variant. The treatment downregulates AChE production and thereby activity. The injury to the CNS may be a head injury (closed or open), brain injury, or spinal cord trauma or other trauma to the CNS.

Abstract: Briefly stated, the invention includes a method of making a transgenic plant that is capable of expressing a physiologically active human acetylcholinesterase, comprising the steps of introducing into at least one plant cell a polynucleotide that encodes a human acetylcholinesterase, and regenerating from the plant cell a transgenic plant that is capable of expressing a physiologically active human acetylcholinesterase in at least one tissue type of the transgenic plant.

Abstract: 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.

Abstract: A pharmaceutical composition for facilitating passage of compounds through the blood-brain barrier comprising the agent ACHE-I4 readthrough (SEQ ID No:1) splice variant or the I4 peptide (SEQ ID No:2) and analogues of each thereof and a pharmaceutically acceptable carrier is disclosed. Alternatively, the pharmaceutical composition for facilitating passage of compounds through the blood-brain barrier can comprise the agents adrenaline, atropine, dopamine and/or an adrenergic combination and a pharmaceutically acceptable carrier. The composition can comprise at least two of the agents. The composition of the present invention can optionally include the compound to be transported across the blood-brain barrier. Alternatively, the compound can be co-administered (simultaneously) with the composition or can be administered at some point during the biologically effective period of the action of the composition.

Abstract: A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-ODN) capable of selectively modulating human acetylcholinesterase (AChE) production and a composition comprising at least one AS-ODN as an active ingredient. A nuclease resistant antisense targeted against the splice junction in the AChE mRNA post-splice message is disclosed. The synthetic nuclease resistant AS-ODNs are capable of selectively modulating human AChE production in the central nervous system or capable of selectively reducing human AChE deposition of the neuromuscular junction. The present invention also provides a method to restore balanced cholinergic signalling in the brain and spinal cord or reduce AChE in the neuromuscular junction in patients in need of such treatment by administering to a patient in need of such treatment a therapeutically effective amount of at least one of the synthetic nuclease resistant AS-ODN capable of selectively modulating human AChE production.

Abstract: A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-OND) capable of selectively modulating human acetylcholinesterase production in the central nervous system is provided. In an embodiment the antisense oligodeoxynucleotide can be selected from5'ACGCTTTCTTGAGGC 3' SEQ ID No:1, or - 5'GGCACCCTGGGCAGC 3' SEQ ID No:2.The present invention also discloses a pharmaceutical or medical composition comprising as active ingredient at least one synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating human acetylcholinesterase production in the central nervous system in a physiologically acceptable carrier or diluent.

Abstract: 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.

Abstract: 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).

Abstract: The invention relates to synthetic phosphorothioated or partially phosphorothioated oligodeoxynucleotides capable of selectively modulating hemopoietic bone marrow cells development. More particularly, the invention relates to synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation condon in human ACHE or 2HS genes, having phosphorothioate bonds linking between the nucleotide bases; synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation condon in human ACHE gene, 2HS gene or BCHE gene or against a 5'-region in the human CHED (cdc2 homolog) gene, having phosphorothioate bonds linking between the four 3'-terminus nucleotide bases. The invention also relates to pharmaceutical compositions comprising as active ingredient at least one synthetic phosphorothioated or partially phosphorothioated antisense oligodeoxynucleotides according to the invention in physiologically acceptable carrier in diluent.

Abstract: 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.

Abstract: Genetically engineered human acetylcholinesterase and antibodies that def the protein are described. These composition may be used in pharmaceutical preparations for treatment and prophylaxis of organo-phosphorous compound poisoning or post-operative apnea. Also described are human cholinesterase DNA probes which may be employed for diagnosing progressing ovarian carcinomas and hemocytopoietic disorders.

Abstract: This invention is directed to genetically engineered proteins having human ChE activity, and more particularly, the activity of human AChE or human pseudo-ChE. The invention also provides for DNA sequences encoding such proteins, and more specifically DNA sequences comprising the entire coding region for encoding such complete proteins, and DNA expression vectors comprising such sequences. The invention also provides for DNA, which as been joined outside living cells, capable of infecting culturable cells, to be maintained therein and in progenies thereof which is adapted to encode such active proteins. The invention further provides culturable cells infected with recombinant DNA defined above, and to purified proteins having human ChE activity produced by such cells. There are further provided antibodies interacting with human AChE and pseudo-ChE and assays based on the use of such antibodies.