Compositions and methods for modulation of extracellular vesicle release and treatment of neurological disorders
Inventors
Kashanchi, Fatah • DeMarino, Catherine
Assignees
George Mason University • George Mason Research Foundation Inc
Publication Number
US-12208080-B2
Publication Date
2025-01-28
Expiration Date
2039-10-16
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
This disclosure relates to methods and compositions for inhibiting release of extracellular vesicles from a cell infected by a virus. One aspect of the disclosure relates to methods for treating viral diseases, reducing damage to a neuron from the central neural system (“CNS”) and/or treating neuroinflammation in a subject. In another aspect, provided herein are methods for inhibiting transcription of a viral RNA and/or release of extracellular vesicles from a cell infected by a virus.
Core Innovation
This disclosure provides pharmaceutical compositions and methods for the inhibition of extracellular vesicle (EV) release from cells infected by viruses, particularly human immunodeficiency virus (HIV) and human T-cell leukemia-lymphoma virus (HTLV). The compositions include a cannabinoid product, such as tetrahydrocannabinol (THC), cannabidiol (CBD), or related cannabinoids, and in some embodiments may additionally include azidothymidine, an interferon (IFN), or a tetracycline antibiotic. The invention also relates to methods for treating viral diseases, reducing neuronal damage in the central nervous system (CNS), and managing neuroinflammation in subjects by using these compositions.
A central problem addressed by the invention is the contribution of EVs to the pathogenesis of various diseases including viral infections and neurodegenerative disorders. EVs can carry viral proteins and nucleic acids, facilitating disease progression and neuroinflammation, as seen in disorders like HIV-associated neurocognitive disorder (HAND) and HIV-associated dementia (HAD). Existing compounds for reducing EV release have limitations such as poor specificity, low solubility, and inability to cross the blood-brain barrier, necessitating improved modulators of EV release with suitable therapeutic properties.
The core innovation involves the discovery that specific cannabinoid products, alone or combined with agents like azidothymidine, IFN, or tetracycline antibiotics, can significantly inhibit the release of EVs from virally infected cells without affecting the size of the vesicles. This effect is observed in various cell types relevant to neurological disease, such as neurons, astrocytes, oligodendrocytes, and microglia, with reduction of viral and inflammatory cargo packaged into the EVs. The compositions and methods provided not only modulate EV release but also inhibit viral RNA transcription and can serve in treating viral diseases and associated neurological damage.
Claims Coverage
The patent contains several independent claims, each highlighting one or more inventive features with respect to compositions and methods for modulating extracellular vesicle release in the context of viral infection and neurological disorders.
Pharmaceutical composition comprising cannabinoid product for inhibiting EV release
A pharmaceutical composition comprising a cannabinoid product in an effective amount sufficient to inhibit release of extracellular vesicles from a cell infected by a virus, where the cell is a neuron, astrocyte, oligodendrocyte, or microglia, and the virus is HIV or HTLV.
Method for treating viral disease using the cannabinoid composition
A method for treating a viral disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a cannabinoid product that inhibits release of extracellular vesicles from a neuron, astrocyte, oligodendrocyte, or microglia, where the virus is HIV or HTLV.
Method for reducing neuronal damage or treating neuroinflammation
A method of reducing damage to a neuron from the central neural system or treating neuroinflammation in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising a cannabinoid product sufficient to inhibit release of extracellular vesicles from a cell infected by HIV or HTLV.
Method for inhibiting transcription of viral RNA
A method of inhibiting transcription of a viral RNA by contacting a cell with the pharmaceutical composition comprising a cannabinoid product.
Method for inhibiting EV release from a cell infected by a virus
A method of inhibiting release of extracellular vesicles from a cell infected by a virus, comprising contacting the cell with the pharmaceutical composition comprising a cannabinoid product, where the extracellular vesicles may be exosomes and/or microvesicles.
These inventive features collectively claim pharmaceutical compositions comprising cannabinoid products for the inhibition of EV release from virally infected neural and glial cells, along with methods for treating viral diseases, neuroinflammatory conditions, reducing neuronal damage, and blocking viral RNA transcription.
Stated Advantages
The compositions can overcome shortcomings of previous EV release modulators, such as poor specificity, low solubility, and blood-brain barrier impermeability.
Inhibition of EV release from virally infected cells can suppress or control the spread of viral components delivered by EVs, potentially reducing disease progression and neuroinflammation.
Cannabinoid products are highly lipophilic and suitable for treatment of CNS viral complications due to their ability to cross the blood-brain barrier.
The pharmaceutical composition can inhibit incorporation of viral components into EVs before release, reducing spread and pathogenicity of viral elements.
The methods can reduce neuronal damage or neuroinflammation caused by viral infections, with potential application in managing neurocognitive disorders such as HAND and HAD.
Documented Applications
Treating viral diseases by administering a pharmaceutical composition that inhibits release of extracellular vesicles from infected cells.
Treating neurological disorders associated with viral infection, including Alzheimer's disease, multiple sclerosis, stroke, and HIV-associated neurocognitive disorders such as asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia, minor cognitive motor disorder, HIV-associated myelopathy, and HIV-associated peripheral neuropathy.
Reducing damage to neurons of the central nervous system or treating neuroinflammation caused by viral infection.
Inhibiting transcription of viral RNA in cells infected by HIV or HTLV.
Inhibiting release of extracellular vesicles (including exosomes and microvesicles) from cells infected by HIV or HTLV.
Interested in licensing this patent?