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Show moreField of the invention: The present invention relates to methods and compositions for treating Alzheimer's disease and other diseases and conditions with an inflammatory component (e.g., central nervous system injury). In particular, the present invention provides agents that regulate the production of proinflammatory and neurotoxic products involved in Alzheimer's disease and other inflammatory diseases. Background of the invention: Alzheimer's disease (AD) is a complex multi-genic neurodegenerative disorder characterized by progressive impairments in memory, behavior, language, and visuo-spatial skills, ending ultimately in death. Hallmark pathologies within vulnerable regions include extracellular .beta.-amyloid deposits, intracellular neurofibrillary tangles, synaptic loss, and extensive neuronal cell death. Research on the causes and treatments of Alzheimer's disease has led investigators down numerous avenues. Although many models have been proposed, no single model of AD satisfactorily accounts for all neuropathologic findings as well as the requirement of aging for disease onset. The mechanisms of disease progression are equally unclear. Considerable human genetic evidence has implicated alterations in production or processing of the human amyloid precursor protein (APP) in the etiology of the disease. Intensive research has proven that AD is a multifactorial disease with many different, perhaps overlapping, etiologies. To date, Alzheimer's disease is the third most expensive disease in the United States, costing society approximately $100 billion each year. It is one of the most prevalent illnesses in the elderly population, and with the aging of society, will become even more significant. Costs associated with AD include direct medical costs such as nursing home care, direct nonmedical costs such as in-home day care, and indirect costs such as lost patient and care giver productivity. Medical treatment may have economic benefits by slowing the rate of cognitive decline, delaying institutionalization, reducing care giver hours, and improving quality of life. Pharmacoeconomic evaluations have shown positive results regarding the effect of drug therapy on nursing home placement, cognition, and care giver time. Thus far, the therapeutic strategies attempted have targeted neurotransmitter replacement, or the preservation of normal brain structures, which potentially provide short-time relief, but do not prevent neuronal degeneration and death. Thus, there is a need for therapies that prevent neuronal degeneration and death associated with Alzheimer's disease and provide long-term relief. Summary of the invention: The present invention relates to methods and compositions for treating Alzheimer's disease and other diseases and conditions with an inflammatory component (e.g., central nervous system injury).
http://www.google.com/patents?vid=USPAT6191154
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Show moreBackground of the invention: The present invention relates to "activated" immature astrocytes and the method of utilizing the activated immature astrocytes in injectable form or on nitrocellulose polymer as a means for reducing secondary necrosis and glial scar formation in lesions in the brain and spinal cord as well as promoting directed blood vessel and axon growth and/or regeneration. The activated immature astrocytes and pharmaceutical compositions comprising same, may be used to treat disorders of the nervous system resulting from accidents or diseases which have in some way damaged the nerve tissue. In the central nervous system the chief non-nervous cells are the glial cell types. These vary in numbers and type from one part of the nervous system to another, but the two basic classes can be distinguished by their size and embryonic origin, namely the marcroglia, i.e. which are relatively large cells derived from the neural plate, and the smaller microglia which stem from the mesodermal tissues surrounding the nervous system. The microglia comprise two cell types, the astrocytes (astroglial cells) and the oligodendrocytes (oligodendroglial cells). The present invention is directed to the use of the former, i.e. astroglial cells, in their immature "activated" state, to reduce both secondary cell death and glial scar formation and promote axon regeneration and blood vessel growth. Astrocytes possess small cell bodies (the nucleus is about 8 mm in diameter in man) with ramifying dendrite-like extensions. The cytoplasmic processes of astrocytes carry fine, foliate extensions which partly engulf and separate neurons and their neurites, and often end in plate-like expansions on blood vessels, ependyma and on the pial surface of the central nervous system. The functions of astrocytes are numerous. They act mechanically as a supporting component of the nervous system. Their microfilaments, microtubules, and surface contact zones fit them for this task. They also act defensively by phagocytosing foreign material or cell debris. They can function as antigen presenting cells to macrophages and can provide a means of limited repair by forming glial scar tissue or filling the gaps left by degenerated neurons. In addition, they have essential metabolic functions in regulating the biochemical environment of neurons, providing nutrients, and regulating acid-base levels, etc. Moreover, the astrocytes, which are able to divide in immature and mature animals, pass after mitosis through a series of structural transformations depending on their state of maturity. In areas of brain injury in young or old animals they proliferate (gliosis) to produce neural support. In a penetrating injury to the central nervous system (CNS) of adult mammals, severe tissue damage and secondary necrosis occurs in the region surrounding the wound.
http://www.google.com/patents?vid=USPAT4900553
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Show moreTable of Contents: 1. Introduction 2. Background of the Invention 3. Summary of the Invention 3.1. Definitions 4. Description of the Drawings 5. Detailed Description of the Invention 5.1. Activated Immature Astrocytes 5.2. Methods of Using Activated Immature Astrocytes in the Promotion of Nerve or Blood Vessel Regeneration and/or Scar Reduction 5.2.1. Treatment of Nerve Injury and Disorders 5.2.2. Pharmaceutical Compositions 5.2.3. Modes of Delivery 5.2.3.1. The Use of Polymer Implants 5.2.3.2. The Use of Activated Immature Astrocytes in Conjunction with Surgical Bypass Techniques 6. Example: Activated Immature Astrocytes Promote Neural and Blood Vessel Regeneration and Reduce Scar Formation in the Forebrain 6.1. Materials and Methods 6.1.1. Transportation of Implants and Cellular Coatings 6.1.1.1. Insertion of the Implants 6.1.1.2. Removal of the Implants Plus Their Cellular Coatings 6.1.1.3. Transplantation of the Implants and Their Cellular Coatings To Older Postcritical Period Hosts 6.1.2. Immunohistochemistry 6.1.3. Horseradish Peroxidase Injections 6.1.4. .sup.3 H-thymidine Autoradiography of Transplants 6.2. Results 6.2.1. Determination of the "Critical Period" in Astrocytes for Axon Elongation 6.2.2. Determination of the Location of the Cell Bodies that Contributed Axons to the Implant Surface 6.2.3. Host Glial Response to Nitrocellulose Bridges Implanted at Various Postnatal Ages 6.2.4. Extracellular Matrices Associated With Gliotic Response at Different Ages 6.2.5. Axon Reaction to Flattened Astrocytes in Postnatal Day 2 Neonates Induced by Compressing the Pores of the Implant 6.2.6. Transplantation of Glial-Coated Implants From Neonatal to Post-critical Period Animals 6.2.7. Induced Axon Growth Over Glial Transplants 6.3. Discussion 7. Example: Transplantation of Purified Activated Immature Astrocytes into Postcritical Period Animals 7.1. Materials and Methods 7.1.1. Preparation of Purified Activated Immature Astrocytes 7.1.2. Preparation of Mature (P14or Older) Astrocytes 7.1.3. Seeding of the Nitrocellulose Implants 7.1.4. Implantation of the Glial-Coated Filters 7.1.4.1. In the Forebrain of the Postnatal Day 60 Acallosal Mice 7.1.4.2. In the Dorsal Root Entry Zone of the Spinal Cord of the Postnatal Day 180 or Older Rats 7.1.5. Immunohistochemistry and .sup.3 -Thymidine Autoradiography of the Transplants 7.2. Results 7.2.1. Transplantation of Purified Astrocytes into the Forebrain 7.2.2. Transplantation of Purified Activated Immature Astrocytes into the Dorsal Root of the Spinal Cord 8. Example: Immortalization of the Activated Immature Astrocytes 9. Example: Astrocyte Maturation Reduces Neurite Outgrowth and Neuronal Adhesion in Vitro 9.1. Materials and Methods 9.1.1. Preparation of Purified Astrocytes 9.1.2. Preparation of Cortical Neurons 9.1.3. Quantitation of Neurite Outgrowth 9.1.4. Short Term Neuronal Adhesion Assay 9.1.5. Electron Microscopy 9.2. Results 9.2.1. Neuronal Morphology on Immature and Mature Astrocytes
http://www.google.com/patents?vid=USPAT5202120
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