# US 2010/0166759 A1 · Metallothionein-Derived Peptide Fragments > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0166759 A1 - Document ID: US20100166759A1 - Status: Published application - Kind: A1 - Application number: 12/223,947 - Filed: 2007-02-12 - Published: 2010-07-01 - Earliest claimed: 2006-02-14 - Assignees: University of Tasmania - Inventors: Vladimir Berezin; Elisabeth Bock; Milena Penkowa - Web page: https://patentgrep.com/patent/US20100166759A1 ## CPC - C07K 14/825: Metallothioneins - A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/04: Anorexiants; Antiobesity agents - A61P 3/06: Antihyperlipidemics - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/06: Antiarrhythmics - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 11/06: Antiasthmatics - A61P 13/12: of the kidneys - A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis - A61P 17/00: Drugs for dermatological disorders - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 19/00: Drugs for skeletal disorders - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents - A61P 19/10: for osteoporosis - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 21/04: for myasthenia gravis - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/02: for peripheral neuropathies - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 25/16: Anti-Parkinson drugs - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/22: Anxiolytics - A61P 25/24: Antidepressants - 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 - A61P 25/32: Alcohol-abuse - A61P 27/02: Ophthalmic agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/04: Antibacterial agents - A61P 31/12: Antivirals - A61P 31/14: for RNA viruses - A61P 31/20: for DNA viruses - A61P 31/22: for herpes viruses - A61P 33/06: Antimalarials - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - A61P 39/02: Antidotes - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract The present invention relates to neural cell survival, differentiation and proliferation promoting peptide fragments derived from metallothioneins (MT), pharmaceutical compositions comprising said peptide fragments and uses thereof for treatment of diseases and conditions where the effects of stimulating neural cell proliferation, differentiation and/or survival, and/or stimulating neural plasticity associated with learning and memory are beneficial for treatment. ## Claims ### Claim 1 A peptide comprising at most 25 contiguous amino acid residues comprising an amino acid motif of the formula: S/D/E-(x)n-S/D/E-K/S, wherein (x)n is a sequence of any amino acid residues, and n is an integer from 4 to 6. ### Claim 2 (depends on 1) The peptide according to claim 1, wherein n is 4. ### Claim 3 (depends on 1) The peptide according to claim 1, wherein n is 6. ### Claim 4 (depends on 2) The peptide according to claim 2, wherein the amino acid sequence (x) comprises at least one of the following amino acid residues: K, S, E or C. ### Claim 5 (depends on 1) The peptide according to claim 1, wherein the peptide comprises an amino sequence of about 10 amino acid residues comprising the motif of claim 1, said amino acid sequence comprising at least one amino acid residue G. ### Claim 6 (depends on 1, 5) The peptide according to claim 5, wherein amino acid residue G precedes an amino acid residue S/D/E of the motif of claim 1. ### Claim 7 (depends on 6) The peptide according to claim 6, wherein one of two amino acid residues S/D/E of the motif is substituted for amino acid residue C. ### Claim 8 (depends on 1) The peptide according to claim 1, wherein the peptide comprises about 15 amino acid residues. ### Claim 9 (depends on 8) The peptide according to claim 8, said peptide comprising an amino acid sequence selected from the following sequences: KKSSCSCSPVGSAK (SEQ ID NO: 1) AQGSISKGASDKSS (SEQ ID NO: 2) MDPNSSSAAGDSST (SEQ ID NO: 3) SAGSSKSKESKSTS (SEQ ID NO: 4) AQGSICKGASDKSS (SEQ ID NO: 5) MDPNCSCAAGDSST (SEQ ID NO: 6) SAGSCKCKESKSTS (SEQ ID NO: 7) KGGEAAEAEAEK, (SEQ ID NO: 8) or a fragment, or a variant thereof. ### Claim 10 (depends on 9) The peptide according to claim 9, wherein the amino acid sequence is homologous to a subsequence of a protein of the metallothionein family of proteins, said protein is selected from human metallothionein-1 A (MT1A), metallothionein-1B (MT1B), metallothionein-1E (MT1E), metallothionein-1F (MT1F), metallothionein-1G (MT1G), metallothionein-1H (MT1H), metallothionein-1I (MT1I), metallothionein-1 K (MT1K), metallothionein-1 L (MT1L), metallothionein-1R (MT1R), metallothionein-1X (MT1 X), metallothionein-2 (MT2), metallothionein-3 (MT3) or metallothionein-4 (MT4). ### Claim 11 (depends on 10) The peptide according to claim 10, wherein the subsequence comprises one of the following amino acid sequences: KKSCCSCCPMSCAK (SEQ ID NO: 9) KKCCCSCCPVGCAK (SEQ ID NO: 10) KKSCCSCCPVGCAK (SEQ ID NO: 11) KKSCCSCCPVGCSK (SEQ ID NO: 12) KKSCCSCCPVGCAK (SEQ ID.NO: 13) KKSCCSCCPLGCAK (SEQ ID NO: 14) KKSCCSCCPVGCAK (SEQ ID NO: 15) KKSCCSCCPVGCAK (SEQ ID NO: 16) KKSCCSCCPVGCAK (SEQ ID NO: 17) KKSCCSCCPMGCAK (SEQ ID NO: 18) KKSCCSCCPVGCAK (SEQ ID NO: 19) KKSCCSCCPVGCAK (SEQ ID NO: 20) KKSCCSCCPAECEK (SEQ ID NO: 21) RKSCCPCCPPGCAK (SEQ ID NO: 22) AQGCICKGASEKCS (SEQ ID NO: 23) AQGCVCKGSSEKCS (SEQ ID NO: 24) AQGCVCKGASEKCS (SEQ ID NO: 25) AQGCVCKGASEKCS (SEQ ID NO: 26) AQGCICKGASEKCS (SEQ ID NO: 27) AQGCICKGASEKCS (SEQ ID NO: 28) AQGCICKGASEKCS (SEQ ID NO: 29) AQGCICKGASEKCS (SEQ ID NO: 30) AQGCICKGTSDKCS (SEQ ID NO: 31) AQGCVCKGASEKCS (SEQ ID NO: 32) AQGCICKGTSDKCS (SEQ ID NO: 33) AQGCICKGASDKCS (SEQ ID NO: 34 AKDCVCKGGEAAEAEAEKCS (SEQ ID NO: 35) ARGCICKGGSDKCS (SEQ ID NO: 36) MDPNCSCATGGSCT (SEQ ID NO: 37) MDPNCSCTTGGSCA (SEQ ID NO: 38) MDPNCSCATGGSCT (SEQ ID NO: 39) MDPNCSCAAGVSCT (SEQ ID NO: 40) MDPNCSCAAGVSCT (SEQ ID NO: 41) MDPNCSCEAGGSCA (SEQ ID NO: 42) MDPNCSCAAGVSCT (SEQ ID NO: 43) MDPNCSCAAAGVSCT (SEQ ID NO: 44) MDPNCSCSPVGSCA (SEQ ID NO: 45) MDPNCSCATGGSCS (SEQ ID NO: 46) MDPNCSCDPVGSCA (SEQ ID NO: 47) MDPNCSCAAGDSCT (SEQ ID NO: 48) MDPETCPCPSGGSCT (SEQ ID NO: 49) MDPRECVCMSGGICM (SEQ ID NO: 50) CTGSCKCKECKCNS (SEQ ID NO: 51) CAGSCKCKECKCTS (SEQ ID NO: 52) CAGSCKCKECKCTS (SEQ ID NO: 53) CAGSCKCKECKCTS (SEQ ID NO: 54) CASSCKCKECKCTS (SEQ ID NO: 55) CAGSCKCKKCKCTS (SEQ ID NO: 56) CAGSCKCKECKCTS (SEQ ID NO: 57) CASSCKCKECKCTS (SEQ ID NO: 58) CAGSCKCKECKCTS (SEQ ID NO: 59) CASSCKCKECKCTS (SEQ ID NO: 60) CAGSCKCKECKCTS (SEQ ID NO: 61) CAGSCKCKECKCTS (SEQ ID NO: 62) CADSCKCEGCKCTS (SEQ ID NO: 63) CGDNCKCTTCNCKT. (SEQ ID NO: 64) ### Claim 12 (depends on 10) The peptide according to claim 10, wherein the subsequence is an amino acid sequence selected from any of the sequences identified as SEQ ID NOs:9-22. ### Claim 13 (depends on 10) The peptide according to claim 10, wherein the subsequence is an amino acid sequence selected from any of the sequences identified as SEQ ID NOs:23-36. ### Claim 14 (depends on 10) The peptide according to claim 10, wherein the subsequence is an amino acid sequence selected from any of the sequences identified as SEQ ID NOs:37-50. ### Claim 15 (depends on 10) The peptide according to claim 10, wherein the subsequence is an amino acid sequence selected from any of the sequences identified as SEQ ID NOs: 51-64. ### Claim 16 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1A, said subsequence is selected from SEQ ID NOs:9, 23, 37 or 51. ### Claim 17 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1B, said subsequence is selected from SEQ ID NOs:10, 24, 38 or 52. ### Claim 18 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1E, said subsequence is selected from SEQ ID NOs:11, 25, 39 or 53. ### Claim 19 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1F, said subsequence is selected from SEQ ID NOs:12, 26, 40 or 54. ### Claim 20 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1G, said subsequence is selected from SEQ ID NOs:13, 27, 41 or 55. ### Claim 21 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1H, said subsequence is selected from SEQ ID NOs:14, 28, 42 or 56. ### Claim 22 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1I, said subsequence is selected from SEQ ID NOs:15, 29, 43 or 57. ### Claim 23 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1K, said subsequence is selected from SEQ ID NOs:16, 30, 44 or 58. ### Claim 24 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1L, said subsequence is selected from SEQ ID NOs:17, 31, 45 or 59. ### Claim 25 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1R, said subsequence is selected from SEQ ID NOs:18, 32, 46 or 60. ### Claim 26 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT1X, said subsequence is selected from SEQ ID NOs:19, 33, 47 or 61. ### Claim 27 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT2, said subsequence is selected from SEQ ID NOs:20, 34, 48 or 62. ### Claim 28 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT3, said subsequence is selected from SEQ ID NOs:21, 35, 49 or 63. ### Claim 29 (depends on 10) The peptide according to claim 10, wherein the amino acid sequence is homologous to a subsequence of MT4, said subsequence is selected from SEQ ID NOs:22, 36, 50 or 64. ### Claim 30 (depends on 1) The peptide according to claim 1, wherein the peptide is capable of binding to a receptor and/or stimulating cell survival and/or cell differentiation and/or cell plasticity associated with memory and learning and/or inhibiting inflammation. ### Claim 31 (depends on 30) The peptide according to claim 30, wherein the cell is a cell of the neural system. ### Claim 32 (depends on 31) The peptide according to claim 31, wherein the cell is a neuronal cell. ### Claim 33 (depends on 30) The peptide sequence according to claim 30, wherein the receptor is megalin. ### Claim 34 (depends on 30) The peptide sequence according to claim 30, wherein the receptor is metallothionein (MT). ### Claim 35 (depends on 34) The peptide according to claim 34, wherein the metallothionein is selected from human metallothionein-1 A (MT1A), metallothionein-1B (MT1B), metallothionein-1E (MT1E), metallothionein-1F (MT1F), metallothionein-1G (MT1G), metallothionein-1H (MT1H), metallothionein-1I (MT1I), metallothionein-1 K (MT1K), metallothionein-1 L (MT1L), metallothionein-1R (MT1R), metallothionein-1X (MT1 X), metallothionein-2 (MT2), metallothionein-3 (MT3) or metallothionein-4 (MT4). ### Claim 36 (depends on 35) The peptide according to claim 35, wherein the metallothionein is MT2. ### Claim 37 (depends on 1) The peptide according to claim 1, wherein the peptide comprises an amino acid sequence selected from SEQ ID NOs:1-64, or a fragment or a variant of said sequence. ### Claim 38 (depends on 9, 37) The peptide according to claim 9 or 37, wherein the variant is an amino acid sequence of at least 6 amino acid residues having at least 65. % sequence similarity with a sequence selected from the sequences of SEQ ID NOs:1-64 and having at least one functional activity of a sequence selected from SEQ ID NOs:1-64. ### Claim 39 A peptide consisting of a sequence selected from SEQ ID NOs 1-8. ### Claim 40 A peptide which is a fragment of a metallothionein, said peptide being a sequence of at most 20 amino acid residues, said sequence is capable of stimulating neurite outgrowth, stimulating neuronal survival, stimulating neural plasticity associated with learning and memory and/or inhibiting inflammation. ### Claim 41 (depends on 40) The peptide according to claim 40, wherein metallothionein is human metallothionein selected from metallothionein-1 A (MT1A), metallothionein-1B (MT1B), metallothionein-1E (MT1E), metallothionein-1F (MT1F), metallothionein-1G (MT1G), metallothionein-1H (MT1H), metallothionein-1I (MT1I), metallothionein-1 K (MT1K), metallothionein-1 L (MT1L), metallothionein-1R (MT1R), metallothionein-1X (MT1 X), metallothionein-2 (MT2), metallothionein-3 (MT3) or metallothionein-4 (MT4). ### Claim 42 (depends on 41) The peptide according to claim 41, said peptide comprising a sequence selected from SEQ ID NOs:9-64 or a fragment or a variant of said sequence. ### Claim 43 (depends on 42) The peptide according to claim 42, said peptide consisting of a sequence selected from SEQ ID NOs:9-64, or a fragment or a variant of said sequence. ### Claim 44 (depends on 1) A compound comprising a peptide according to claim 1. ### Claim 45 (depends on 44) The compound according to claim 44, said compound comprising a single copy of the peptide. ### Claim 46 (depends on 44) The compound according to claim 44, wherein the compound is formulated as a multimer consisting of two or more copies of the peptide, such as a dimer or tetramer. ### Claim 47 (depends on 46) The compound of claim 46, wherein the multimer is a dendrimer. ### Claim 48 (depends on 1, 44) A method of stimulating neurite outgrowth, neural cell survival and/or neural cell plasticity associated with learning and memory comprising administering a peptide according to claim 1 or compound according to claim 44. ### Claim 49 (depends on 1, 44) A method of stimulating neural cell survival, differentiation, proliferation and/or plasticity associated with memory and learning comprising using administering a peptide according to claim 1 or compound according to claim 44. ### Claim 50 (depends on 1, 44) Method of treatment of a condition or disease comprising administering to an individual in need thereof an effective amount of a peptide according to claim 1 or a compound according to claim 44. ### Claim 51 (depends on 50) The method according to claim 50, wherein stimulating neural cell survival, differentiation, proliferation and/or plasticity is beneficial for treatment. ### Claim 52 (depends on 51) The method according to claim 51, wherein the condition or disease is a condition or disease of the central and peripheral nervous system. ### Claim 53 (depends on 51) The method according to claim 51, wherein the condition or disease is selected from postoperative nerve damage, traumatic nerve damage, impaired myelination of nerve fibers, postischaemic damage, nerve degeneration associated with diabetes mellitus, disorders affecting the circadian clock or neuro-muscular transmission. ### Claim 54 (depends on 50) The method according to claim 50, wherein the condition or disease is selected from of conditions or diseases of the muscles including conditions with impaired function of neuro-muscular connections. ### Claim 55 (depends on 50) The method according to claim 50, wherein the condition or disease is cancer. ### Claim 56 (depends on 55) The method according to claim 55, wherein the cancer is any cancer involving neoangiogenesis. ### Claim 57 (depends on 55) The method according to claim 55, wherein the cancer is a cancer of the nervous system. ### Claim 58 (depends on 51) The method according to claim 51, wherein the condition or disease is an impaired ability to learn and/or impaired memory. ### Claim 59 (depends on 58) The method according to claim 58, wherein the condition or disease is Parkinson's disease, Alzheimer's disease, Huntington's disease or dementia. ### Claim 60 (depends on 51) The method according to claim 51, wherein the condition or disease is a mental disease, neuropsychiatric disorders including bipolar (BPD), genetically related unipolar affective disorders, delusional disorders, paraphrenia, paranoid psychosis, schizophrenia, schizotypal disorder, schizoaffective disorder, schizoaffective bipolar and genetically related unipolar affective disorders, psychogenic psychosis, catatonia, periodic bipolar and genetically related unipolar affective disorders, cycloid psychosis, schizoid personality disorder, paranoid personality disorder, bipolar and genetically related unipolar affective disorders related affective disorders and subtypes of unipolar affective disorder. ### Claim 61 (depends on 50) The method according to claim 50, wherein the condition or disease is body damage due to alcohol consumption. ### Claim 62 (depends on 50) The method according to claim 50, wherein the condition or disease is a prion disease. ### Claim 63 (depends on 50) The method according to claim 50, wherein the condition or disease is characterised by the presence of a sustained inflammatory response. ### Claim 64 (depends on 63) The method according to claim 63, wherein the condition or disease is brain inflammation or autoimmune disease. ### Claim 65 (depends on 63) The method according to claim 63, wherein the condition or disease is Guillain-Barré syndrome, its variant form, or another complement dependent neuromuscular disorder. ### Claim 66 (canceled) ### Claim 67 (depends on 1) An antibody, antigen binding fragment or a variant thereof, capable of recognizing and binding to an epitope comprising the amino acid motif according to claim 1 or peptide according to claim 1. ### Claim 68 (depends on 67) The antibody according to claim 67, wherein the epitope comprises an amino acid sequence selected from SEQ ID NOs:1-64, or a fragment or variant of said sequence. ### Claim 69 (depends on 1, 44) A pharmaceutical composition comprising a peptide according to claim 1 or compound according to claim 44. ### Claim 70 (depends on 67) A pharmaceutical composition comprising an antibody according to claim 67. ### Claim 71 (depends on 1, 44) Method of treatment of a condition or disease comprising administering to an individual in need thereof an effective amount of a peptide according to claim 1, compound according to claim 44 or pharmaceutical composition comprising a peptide according to claim 1 or a compound comprising a peptide according to claim 1. ### Claim 72 (depends on 1, 44, 67) Method for detection of methallothionein protein in a sample comprising using a peptide sequence according to claim 1, a compound according to claim 44 or an antibody according to claim 67. ### Claim 73 (depends on 1, 44, 67) A kit comprising at least one peptide according to claim 1, a compound according to claim 44 and/or an antibody according to claim 67. ### Claim 74 (depends on 73) The kit according to claim 73, wherein the at least one peptide, compound and/or antibody comprise a detectable label. ### Claim 75 (depends on 72) The kit according to claim 72, wherein said kit is for use in a diagnostic method comprising a step of assessing the level of metallothionein in a sample. ### Claim 76 (depends on 1) The peptide according to claim 1, wherein the peptide comprises from 13 to 17 amino acid residues. ### Claim 77 (depends on 51) The method according to claim 51, wherein stimulating plasticity associated with learning and memory is beneficial for treatment. ### Claim 78 (depends on 53) The method according to claim 53, wherein the condition or disease is postischaemic damage, and such postischaemic damage is after stroke. ### Claim 79 (depends on 54) The method according to claim 54, wherein the condition or disease is a condition with impaired function of neuro-muscular connections, and said condition occurs after organ transplantation or as the result of a genetic or traumatic atrophic muscle disorder. ### Claim 80 (depends on 59) The method according to claim 59, wherein the condition or disease is multiinfarct dementia. ### Claim 81 (depends on 60) The method according to claim 60, wherein the condition or disease is a mental disease characterized by a disorder of thought and/or mood. ### Claim 82 (depends on 65) The method according to claim 65, wherein the condition or disease is Miller Fisher syndrome.