Methods of treating and preventing diseases and disorders of the central nervous system
Inventors
McGavern, Dorian B. • Roth, Theodore
Assignees
US Department of Health and Human Services
Publication Number
US-9974801-B2
Publication Date
2018-05-22
Expiration Date
2033-02-05
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Abstract
Disclosed is a method of treating or preventing a disease or disorder of the central nervous system (CNS) in a patient comprising administering transcranially, for example, directly to the skull, an effective amount of an anti-inflammatory agent to the patient. Examples of the anti-inflammatory agent include glutathione and inhibitors of purinergic receptors such as P2X4, P2X7, P2Y6, and P2Y12 receptors. Examples of disease or disorder of the CNS include brain injury, particularly traumatic brain injury, inflammation, infection, degeneration of brain cells, stroke, brain edema, tumor, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Also disclosed is a kit comprising at least one anti-inflammatory agent and printed materials containing instructions for transcranially administering the anti-inflammatory agent to the patient having a disease or disorder of the CNS.
Core Innovation
The invention provides a method of treating or preventing diseases or disorders of the central nervous system (CNS) in a patient by administering transcranially an effective amount of a reactive oxygen scavenger or an anti-inflammatory agent. This method enables the therapeutic agents to penetrate the skull and bypass the blood brain barrier (BBB), rapidly reaching the injured or inflamed CNS areas and establishing a high local concentration of the agent at the injury site.
The disclosed method addresses the problem that many drugs are ineffective in treating CNS diseases such as traumatic brain injury (TBI) due to the inability of systemically administered drugs to cross the BBB and achieve therapeutic concentrations in the CNS. The invention solves this by transcranial administration, for example, direct application to the skull, allowing compounds to diffuse through the porous skull bone, which consists of porous upper cortical, cancellous, and lower cortical layers.
The method includes administering anti-inflammatory agents such as glutathione and inhibitors of purinergic receptors (including P2X4, P2X7, P2Y6, and P2Y12 receptors). The invention also provides methods of inhibiting or reducing formation of reactive microglia, recruitment of neutrophils and monocytes, and reducing the number of dead cells in the brain parenchyma or meninges after traumatic brain injury by transcranial administration of these agents.
Claims Coverage
The patent includes four independent claims detailing methods of treating Parkinson's disease using transcranial administration of an anti-inflammatory agent, specifically glutathione.
Method of treating Parkinson's disease by transcranial administration of glutathione
A method of treating Parkinson's disease in a patient comprising administering an effective amount of glutathione transcranially in an aqueous vehicle, where administration includes direct application to the skull, application through the scalp, or injection into the skull bone.
Administration via transdermal patch
The anti-inflammatory agent glutathione is administered via a transdermal patch placed on the patient's skull or scalp.
Administration via subcutaneous injection under the scalp
Glutathione is administered by subcutaneous injection under the scalp of the patient.
Administration via injection into cancellous bone of the skull
Glutathione is administered by injection into the cancellous bone layer of the skull bone of the patient.
The claims focus on the method of treating Parkinson's disease by transcranially administering glutathione through various routes including direct skull application, transdermal patches, subcutaneous scalp injection, and injection into the skull bone, encompassing multiple modes to deliver the anti-inflammatory agent effectively to the CNS.
Stated Advantages
Allows therapeutic agents to bypass the blood brain barrier, enabling drugs that are otherwise blocked to reach CNS tissue.
Establishes a high local concentration of therapeutic agents rapidly at the injured or inflamed CNS site.
Reduces formation of reactive microglia, recruitment of neutrophils and monocytes, and cell death following traumatic brain injury.
Documented Applications
Treatment or prevention of diseases or disorders of the central nervous system including brain injury, inflammation, infection, degeneration of brain cells, stroke, brain edema, tumor, Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
Treatment of traumatic brain injury arising from sports, armed conflict, brain surgery, or other causes.
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