# US 2021/0275625 A1 · Method of modulating the concentration of proteins in cerebrospinal fluid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275625 A1 - Document ID: US20210275625A1 - Status: Published application - Kind: A1 - Application number: 17/329,685 - Filed: 2021-05-25 - Published: 2021-09-09 - Earliest claimed: 2016-10-03 - Assignees: Richard L. Bowen - Applicants: Richard L. Bowen - Inventors: Richard L. BOWEN; Craig S. ATWOOD - Web page: https://patentgrep.com/patent/US20210275625A1 ## CPC - A61K 38/09: Luteinising hormone-releasing hormone [LHRH] {, i.e. Gonadotropin-releasing hormone [GnRH]}; Related peptides - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - 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 - C07K 16/26: against hormones {; against hormone releasing or inhibiting factors} - C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)} - A61K 2039/505: {comprising antibodies} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - 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 - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Method of modulating the concentrations of tau, P-tau, β-amyloid, NF-L, α-synuclein and/or neurogranin in cerebrospinal fluid (CSF) to prevent, stabilize and/or reverse suitable health conditions. ## Claims ### Claim at position 1 1-16. (canceled) ### Claim 17 A method of treating age-related loss in brain function, the method comprising: measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light (NF-L), total α-synuclein, and neurogranin in the cerebrospinal fluid of a patient suffering from age related cognitive decline in the absence of clinical signs of dementia, wherein the patient is at most 50 years of age, and the β-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43; comparing the measured concentrations of the protein to a median concentration of the protein in a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia; administering an effective dose of a gonadotropin-releasing hormone (GnRH) analog to the patient: if the concentrations of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population; or if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population. ### Claim 18 (depends on 17) The method according to claim 17, wherein administering a gonadotropin-releasing hormone (GnRH) analog to the patient lowers the concentration of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin in the cerebrospinal fluid of the patient to the lower quartile of the reference cognitively normal population, or raises the concentration of β-amyloid in the cerebrospinal fluid of the patient to the upper most quartile of the reference cognitively normal population. ### Claim 19 (depends on 17) The method according to claim 17, further comprising: lowering cerebrospinal fluid (CSF) tau and/or P-tau by inhibiting gonadotropin signaling. ### Claim 20 (depends on 17) The method according to claim 17, wherein the GnRH analog is a leuprolide or its pharmaceutically acceptable salts. ### Claim 21 (depends on 20) The method according to claim 20, wherein the effective dose of leuprolide is from 0.2 to 20 mg/day, 1 to 10 mg/month, or 10 to 50 mg every three months. ### Claim 22 (depends on 20) The method of claim 20, wherein administering the effective dose of leuprolide comprises administering a dose of leuprolide of 1 mg/day, 5 mg/month, or 25 mg every three months. ### Claim 23 A method of preventing age-related loss of brain function, the method comprising: measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light (NF-L), total α-synuclein; and neurogranin in the cerebrospinal fluid of a patient susceptible to suffering from age related cognitive decline in the absence of clinical signs of dementia, wherein the patient is at most 50 years of age, and the β-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43; comparing the measured concentrations of the protein to a median concentration of the protein in a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia; administering an effective dose of a gonadotropin-releasing hormone (GnRH) analog to the patient: if the concentrations of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population; or if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population. ### Claim 24 (depends on 23) The method according to claim 23, wherein administering the effective dose of a gonadotropin-releasing hormone (GnRH) analog to the patient lowers the concentration of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin in the cerebrospinal fluid of the patient to the lower quartile of the reference cognitively normal population, or raises the concentration of β-amyloid in the cerebrospinal fluid of the patient to the upper most quartile of the reference cognitively normal population. ### Claim 25 (depends on 23) The method according to claim 23, wherein the GnRH analog is a leuprolide or its pharmaceutically acceptable salts to a patient in need thereof. ### Claim 26 (depends on 25) The method according to claim 25, wherein the effective dose of leuprolide is from 0.2 to 20 mg/day, 1 to 10 mg/month, or 10 to 50 mg every three months. ### Claim 27 A method of preventing age-related loss in brain function in a post-menopausal patient with leuprolide, the method comprising: measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light, total α-synuclein, and neurogranin in the cerebrospinal fluid of the patient, wherein the patient is neurologically normal and is at most 50 years of age, and wherein the 3-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43; comparing the measured concentrations of the protein to a median concentration of a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia; administering an effective dose of leuprolide to the patient: if the concentrations of tau, P-tau, neurofilament light, total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population; or if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population or lower than the median concentration of the reference cognitively normal population; wherein the effective dose of leuprolide is from 0.2 to 20 mg/day, 1 to 10 mg/month, or 10 to 50 mg every three months. ### Claim 28 (depends on 27) The method of claim 27, wherein the step of administering an effective dose of leuprolide comprises administering a dose of leuprolide of 1 mg/day, 5 mg/month, or 25 mg every three months.