# US 10,441,573 B2 · DBH inhibitors for treating memory loss > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,573 B2 - Document ID: US10441573B2 - Status: Granted - Kind: B2 - Application number: 16/060,234 - Filed: 2016-12-09 - Published: 2018-12-27 - Granted: 2019-10-15 - Earliest claimed: 2015-12-09 - Assignees: Brandeis University - Applicants: Brandeis University - Inventors: John Lisman - Web page: https://patentgrep.com/patent/US10441573B2 ## CPC - A61K 31/417: Imidazole-alkylamines, e.g. histamine, phentolamine - A61K 31/145: having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155) - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 31/4458: only substituted in position 2, e.g. methylphenidate - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to the use of DBH inhibitors (e.g., disulfiram and Nepicastat), and pharmaceutical compositions thereof, for treating subjects with certain types of memory loss, for instance memory loss associated with a neurodegenerative disease, disorder, or condition, such as Alzheimer's Disease. ## Claims ### Claim 1 A method comprising steps of: administering to a subject suffering from or susceptible to memory loss associated with a neurodegenerative disease, disorder, or conditioner (i) an effective amount of a DBH inhibitor, and (ii) one or more agents that ameliorate noradrenaline reduction associated with use of a DBH inhibitor, such that the severity or incidence of memory loss is reduced, or its onset is delayed. ### Claim 2 (depends on 1) The method of claim 1, wherein the neurodegenerative disease, disorder, or condition is associated with reduced dopamine levels in the locus coeruleus (LC). ### Claim 3 (depends on 1) The method of claim 1, wherein the neurodegenerative disease, disorder, or condition is Alzheimer's Disease. ### Claim 4 (depends on 1) The method of claim 1, wherein the Alzheimer's disease is early stage Alzheimer's Disease. ### Claim 5 A method comprising steps of: administering to a subject suffering from or susceptible to memory loss associated with degeneration of the locus coeruleus (LC) (i) an effective amount of a DBH inhibitor, and (ii) one or more agents that ameliorate noradrenaline reduction associated with use of a DBH inhibitor, such that the severity or incidence of memory loss is reduced, or its onset is delayed. ### Claim 6 (depends on 1) The method of claim 1, wherein the DBH inhibitor is disulfiram or Nepicastat. ### Claim 7 (depends on 1) The method of claim 1, wherein the subject is a mammal. ### Claim 8 (depends on 1) The method of claim 1, wherein the one or more agents that ameliorate noradrenaline reduction associated with use of a DBH inhibitor is L-DOPS. ### Claim 9 (depends on 1) The method of claim 1, further comprising administration of one or more agents or therapies known to increase levels of dopamine in a subject. ### Claim 10 (depends on 9) The method of claim 9, wherein the one or more agents or therapies known to increase levels of dopamine in a subject comprises administration of L-DOPA to the subject. ### Claim 11 (depends on 1) The method of claim 1, further comprising administration of one or more agents and/or therapies known to inhibit reuptake of dopamine in a subject. ### Claim 12 (depends on 11) The method of claim 11, wherein the one or more agents and/or therapies known to inhibit reuptake of dopamine in a subject is selected from the group consisting of altropane (O-587), amfonelic acid (WIN 25978), aminaptine, BTCP (GK-13), DBL-583, difluoropine (O-620), GBR-12783, GBR-12935, GBR-13069, GBR-13098, GYKI-52895, lometopane (beta-CIT, RTI-55), methylphenidate, RTI-229, and vanoxerine (GBR-12909). ### Claim 13 (depends on 1) The method of claim 1, wherein the method prevents or reduces amyloid beta plaque formation as compared to an untreated subject. ### Claim 14 (depends on 1) The method of claim 1, wherein the subject is also undergoing treatment with one or more agents or therapies known to treat Alzheimer's Disease. ### Claim 15 (depends on 1) The method of claim 1, wherein the DBH inhibitor is administered in doses ranging from about 1 mg/kg/day to about 50 mg/kg/day. ### Claim 16 (depends on 1) The method of claim 1, wherein the DBH inhibitor is administered systemically, intravenously, intraperitonealy, or orally. ### Claim 17 (depends on 1) The method of claim 1, wherein the DBH inhibitor is administered orally once or twice daily. ### Claim 18 (depends on 1) The method of claim 1, further comprising the step of monitoring the subject. ### Claim 19 (depends on 1) The method of claim 1, further comprising administration of L-DOPS to the subject. ### Claim 20 (depends on 1) The method of claim 1, wherein the DBH inhibitor is a selective inhibitor.