Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1996-11-13
1999-09-14
Campbell, Eggerton A.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 243, 4353201, C07H 2104, C12N 1500
Patent
active
059524812
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a method for determining a predisposition for and diagnosing the existence of a degenerative disease, particularly, but not exclusively, Alzheimer's Disease (AD), and also products and processes for treating and obtaining treatments for such a degenerative disease. The single inventive concept also relates to products and processes for treating and obtaining treatments for Down's syndrome. In addition, the single inventive concept also relates to a method for determining a predisposition for and diagnosing the existence of cancer, particularly, but not exclusively, papilloma virus induced cancers, and also products and processes for treating and obtaining treatments for such cancers.
In the following application the term degenerative disease will be taken to mean a disease characterised by an aberration in the ubiquitination pathway and/or intermediate filament inclusion bodies of a diverse type such as those found in Parkinson's Disease, Pick's Disease, Alzheimer's Disease, as well as Rosenthal fibres in Cerebellar Astrocytomas, Cytoplasmic bodies in muscle and Mallory bodies in Alcoholic Liver Disease.
The degenerative neurological disease, Alzheimer's Disease, is one of the most challenging medical problems of our day. AD is a chronic, progressive, irreversible and fatal age-related dementia. It has received increased attention in recent years because of current demographic data, which data shows a continuously increasing proportion of elderly people within the population. The disease appears to be specific for humans and aged primates only and its causes are largeiy unknown. The disease presents a major public health problem in that caring for demented patients is particularly demanding on health care resources.
Studies of the disease are complicated by the fact that a reliable diagnosis depends on analysis of brain tissue, suicIh diagnosis usually being conducted post-mortem and being of no use to the patient concerned. Putative clinical diagnosis is made principally bv exclusion of other causes of dementia--a largely unsatisfactory situation.
Studies are further hindered by the fact that useful animal or cell models are not yet available for investigation. Hence the development of therapeutic agents for treating the disease is not vet possible.
An understanding of the disease is further complicated by the fact that in some cases AD is familial, whereas in other cases it is sporadic. However, in all instances post-mortem diagnosis is determined by the distinctive neuropathological features of the disease. These features comprise two conspicuous types of deposits; amyloid plaques and neurofibrillary tangles (NFTs). The plaques consist of aggregates of a peptide derived from amyloid precursor transmembrane protein (APP). The plaques are generated by abnormal protein metabolism. NFTs and their constituents, the paired helical filaments (PHFs) consist largely of a microtubular-associated protein, known as tau, in various abnormal states of phosphorylation. It is known that PHFs are very highly insoluble and this makes their analysis and characterisation extremely difficult. In addition, it is known that NFTs are associated with the protein ubiquitin; however, the significance of this association is unknown. That ubiquitin is a component of paired helical filaments was first disclosed in 1987. It is also known that ubiquitin is a common factor in intermediate filament inclusion bodies of a diverse type in man such as those found in Parkinson's Disease, Pick's Disease, Alzheimer's Disease as well as Rosenthal fibres in Cerebellar Astrocytomas, cytoplasmic bodies in muscle and Mallory bodies in Alcoholic Liver Disease. However, the significance of these associations is unknown.
It is also interesting to note that the pathology of AD is also found in victims of Down's syndrome. The significance of this will be described in greater detail hereinafter.
It is, however, known that the ubiquitination pathway functions to target cellular proteins for degradation. The pathway is thought to o
REFERENCES:
patent: 5384255 (1995-01-01), Ciechanover et al.
Structural and Functional Conservation of Two Human Homologs of Yeast DNA Repair Gene RAD6, Proc. Natl. Acad. Sci. USA, (Biochemistry), vol. 88, pp. 8865-8869 (1991), M.Koken et al.
cDNA Cloning of Novel Human Ubiquitin Carrier Protein, The Journal of Biological Chemistry, vol. 267, No. 22 pp. 15829-15835 (1992), Z. Liu et al.
Cloning of the Human Homolog of the CDC34 Cell Cycle Gene by Complementation in Yeast, Proc. Natl. Acad. Sci USA (Genetics), vol. 90, pp. 10484-10488 (1993), S. E. Plon et al.
A Human Ubiquitin-Conjugating Enzyme Homologous to Yeast UBC8, The Journal of Biological Chemistry, vol. 269, No. 12, pp. 8797-8802, (Mar., 1994), P. Kaiser et al.
Homologs of the Essential Ubiquitin Conjugating Enzymes UBC1, 4 and 5 in Yeast are Encoded by a Multigene Family in Arabidopsis Thaliana, The Plant Journal, 3(4), pp. 545-552, (1993), Girod et al.
Purification and Characterization of a Novel Species of Ubiquitin-Carrier Protein, E2, That Is Involved in Degradation of Non-"N-end Rule" Protein Substrates, The Journal of Biological Chemistry, vol. 269, pp. 9574-9581, (Apr. 1994), N. Blumenfeld et al.
Cloning of a Gene Bearing Missense Mutations in Early-Onset Familial Alzheimer's Disease, Nature, vol. 375, pp. 754-760 (Jun. 1995) R. Sherrington et al.
Identification of a Human Ubiquitin-Conjugating Enzyme that Mediates the E6-Ap-dependent Ubiquitination of p53, Proc. Natl. Acad. Sci USA (Biochemistry), vol. 91, pp. 8797-8801, (Sep. 1994) M. Scheffner et al.
Degradation of the Tumor Suppressor Protein p53 by the Ubiquitin-Medicated Proteolytic System Requires a Novel Species of Ubiquitin-Carrier Protein, E2, Journal of Biological Chemistry, vol. 269, pp. 9582-9589, (Apr. 1994), A. Ciechanover et al.
Markham Alexander Fred
Robinson Philip Alan
Campbell Eggerton A.
The University of Leeds
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