Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving viable micro-organism
Patent
1995-05-22
1998-08-04
Leary, Louise
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving viable micro-organism
435 29, 435 39, 435 4, 4352402, 43524023, 435 41, 436 63, 514462, 514629, 540 478, 549345, C12Q 124, C12Q 102, C12Q 110, C12N 500
Patent
active
057891893
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to cystic diseases. More specifically, the invention relates to the use of a culture of cells that form cysts in vitro, to a method of screening for agents which can treat such diseases, and to pharmacological treatments of the diseases.
BACKGROUND OF THE INVENTION
Cytoskeletal Components of the Cell
The cytoskeleton plays an important role in the growth, division, and migration of eukaryotic cells. Changes in cellular morphology, the repositioning of internal organelles, and cellular migration all depend on complex networks of protein filaments that traverse the cytoplasm.
These protein filaments fall into three main categories according to their size: microtubules, intermediate filaments, and microfilaments. Both microtubules and microfilaments are made of globular subunits which can quickly polymerize and depolymerize in the cell resulting in movement and morphological changes. Intermediate filaments are made of fibrous protein subunits and tend to be more stable with longer half-lives than most microtubules and microfilaments.
Current theory holds that cells have a pool of unpolymerized globular subunits in the cytoplasm which is used to rapidly form the cytoskeletal microtubules and microfilaments. Microtubules are formed by a dimer of tubulin proteins which take on a helical shape to form filaments. Similarly, microfilaments comprise actin proteins which agglutinate together to form elongated filaments. In addition to these fibers, the cytoskeleton is also made up of many other components for linking the filaments to each other or to the plasma membrane. Many cytoplasmic components can influence the rate of filament polymerization or depolymerization. Also, drugs have been discovered which affect the rate of filament polymerization and lead to either abnormal accumulations of protein filaments or unpolymerized globular subunits.
Taxol, colchicine, vinblastine, cytochalasin-B, and cytochalasin-D are all well known disruptors of cytoskeletal development. Taxol inhibits depolymerization of the microtubule filaments, while vinblastine and colchicine inhibit microtubule polymerization. Griseofulvin is another drug that interferes with microtubule function, although the mechanism of this interference is not yet established. Cytochalasin-B and cytochalasin-D are inhibitors of microfilament networks.
Diseases Involving Cyst Formation
There are many human diseases which result in the formation of cysts which contain either semi-solid or fluid material. The contents of a cyst sometimes derive from normally retained fluid (e.g. a sebaceous cyst can contain fluid from a blocked sebaceous gland) or from a parasitic infection. Benign cysts can occur in the ovary, spleen, lungs, kidney and liver, where they are often congenital. Some congenital cysts result from fetal malformations and developmental failure while others are direct results of a disease state.
The polycystic kidney diseases (PKD) are a group of disorders characterized by a large number of cysts distributed throughout dramatically enlarged kidneys. The resultant cyst development leads to impairment of kidney function and can eventually cause kidney failure. In humans, PKD can be inherited in autosomal dominant (ADPKD) or autosomal recessive (ARPKD) forms.
ADPKD is the most common dominantly inherited kidney disease of humans, while ARPKD occurs relatively rarely. Clinically, ADPKD represents a major cause of chronic renal failure in humans and accounts for 10% of all patients requiring chronic dialysis or renal transplantation. Currently, 500,000 Americans and 5 million people worldwide are estimated to be afflicted with PKD. In the U.S. this represents an annual health care cost of nearly one billion dollars.
PKD probably begins in utero in most patients with the kidneys increasing in size and ultimately showing signs of disease in the fourth or fifth decade of life. At present there are methods of detecting PKD in utero. Approximately 25% of patients do not have a family history consistent wit
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Leary Louise
The Regents of the University of California
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