Recombinant T-cell receptor ligand for the treatment of cognitive and neuropsychiatric impairment induced by substance addiction
Inventors
Vandenbark, Arthur A. • Burrows, Gregory G.
Assignees
Oregon Health and Science University • US Department of Veterans Affairs
Publication Number
US-8895018-B2
Publication Date
2014-11-25
Expiration Date
2032-01-30
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Abstract
Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II β1 domain and the second domain is an MHC class II α1 domain; or wherein the first domain is an MHC class I α1 domain and the second domain is an MHC class I α2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.
Core Innovation
This invention provides methods for the treatment of cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. The methods involve administering a therapeutically effective amount of a major histocompatibility complex (MHC) molecule that includes covalently linked first, second, and third domains. Specifically, the MHC molecule comprises either a class II β1 domain linked to an α1 domain or a class I α1 domain linked to an α2 domain, with the third domain covalently linked to the first domain and comprising an antigen of the central or peripheral nervous system.
The problem addressed is that substances such as methamphetamine cause long-term structural damage to brain regions controlling cognitive and neuropsychiatric functions, and currently there are no FDA-approved pharmacotherapies for such addiction-induced impairments. Relapse rates remain high following existing treatments, largely due to persistent cognitive impairments and neuropsychiatric effects. Therefore, new interventions are needed to help adults regain lost cognitive function and reduce relapse following addiction and remission.
The disclosure describes use of recombinant T cell receptor ligands (RTLs) that mimic MHC function, particularly recombinant polypeptides including class II β1 and α1 domains or class I α1 and α2 domains, optionally linked to antigens such as myelin proteins of the central or peripheral nervous system. These RTLs may treat or improve cognitive or neuropsychiatric impairment induced by substance addiction, including addiction to sympathomimetic substances like methamphetamine or cocaine, opioids, or alcohol. The methods may also include measuring cognitive or neuropsychiatric function and optionally administering additional therapies.
Claims Coverage
The claims cover two independent claims focusing on the recombinant T cell receptor ligand (RTL) molecule and its pharmaceutical composition for treatment.
Isolated recombinant T cell receptor ligand (RTL) molecule
An isolated recombinant T cell receptor ligand consisting of the specific amino acid sequence of SEQ ID NO: 1, which includes covalently linked MHC class II β1 and α1 domains linked to an antigenic peptide from the central nervous system.
Pharmaceutical composition comprising RTL
A pharmaceutical composition that comprises a therapeutically effective amount of the isolated RTL molecule (SEQ ID NO: 1) and a pharmaceutically acceptable carrier suitable for therapeutic administration.
The claims focus on the isolated recombinant T cell receptor ligand molecule having a defined amino acid sequence and the pharmaceutical composition containing it as the active component to treat cognitive or neuropsychiatric impairment induced by substance addiction.
Stated Advantages
The disclosed methods provide new interventions that address cognitive and neuropsychiatric impairments induced by substance addiction, which are not effectively treated by current pharmacotherapies, such as for methamphetamine addiction.
Treatment with the recombinant MHC molecules (RTLs) reduces cognitive impairments and neuropsychiatric effects, thereby potentially lowering relapse rates and improving treatment retention for substance addiction.
The methods allow for restoring or increasing cognitive function in subjects with substance addiction, enabling them to regain lost function and re-engage in meaningful activities, reducing social, economic, and environmental costs.
Documented Applications
Treatment of cognitive or neuropsychiatric impairment induced by substance addiction such as methamphetamine, cocaine, opioid, or alcohol addiction.
Increasing cognitive function in subjects with substance addiction using recombinant MHC molecules covalently linked to antigens of the central or peripheral nervous system.
Use in therapeutic interventions where subjects are administered recombinant T cell receptor ligands to ameliorate addiction-associated cognitive deficits and neuropsychiatric symptoms.
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