Methods of preventing, treating and diagnosing disorders of protein aggregation

• US 20040204387A1
• Filed: 02/26/2004
• Published: 10/14/2004
• Est. Priority Date: 02/27/2003
• Status: Active Grant

• Current Assignee: Joanne Mclaurin
• Original Assignee: Joanne Mclaurin
• Inventors: McLaurin, JoAnne
• Granted Patent: US 7,521,481 B2
• Time in Patent Office: Days
• US Class Current: 514/102
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: G01N 33/60 involving radioactive labelled substances
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Disclosed are methods of preventing, treating, or diagnosing in a subject a disorder in protein folding or aggregation, or amyloid formation, deposition, accumulation, or persistence consisting of administering to said subject a pharmaceutically effective amount of inositol stereoisomers, enantiomers or derivatives thereof.

Claims

1. A method of treating or preventing in a subject a condition of the central or peripheral nervous system or systemic organ associated with a disorder in protein folding or aggregation, or amyloid formation, deposition, accumulation, or persistence comprising administering to said subject a pharmaceutically effective amount of a compound having the following structure:

2. The method of claim 1, wherein said compound is said compound is a 1,2,3,4,5 ,6-cyclohexanehexol.

3. The method of claim 2, wherein said compounds is selected from the group of cis-, epi-, allo-, muco-, neo-, scyllo-, D-chiro- and L-chiro-inositols.

4. The method of claim 1, wherein said compound is a 1,2,3,4,5-cyclohexanepentol.

5. The method of claim 4, wherein said compound is a quercitol selected from the group of epi-, vibo-, scyllo-, allo-, talo-, gala-, cis-, muco-, neo-, proto-quercitols and enantiomers thereof.

6. The method of claim 1, wherein said compound is selected from the group of a cyclohexanetetrol, a cyclohexanetriol, stereoisomer of cyclohexanetetrol, stereoisimer of cyclohexanetriol, enantiomer of cyclohexanetetrol, and enantiomer of cyclohexanetriol.

7. The method of claim 1, wherein said compound is a pentahydroxycyclohexanone or a stereoisomer or an enantoimer thereof.

8. The method of claim 7, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

9. The method of claim 1, wherein said compound is a trihydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

10. The method of claim 9, wherein said compound is (−

)-1-deory-scyllo-inosose.

11. The method of claim 1, wherein said compound is a pentahydroxycyclohexanone, or a stereoisomer or an enantiomer thereof

12. The method of claim 11, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

13. The method of claim 1, wherein said compound is a trihydroxyxcyclohexanone or a stereoisomer or an enantiomer thereof.

14. The method of claim 13, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

15. The method of claim 1, wherein said compound is an 0-monomethyl-cyclohexanehexol or a stereoisomer or an enantiomer thereof.

16. The method of claim 15, wherein said compound is selected from the group of D-pinitol, L-quebrachitol and D-bornesitol.

17. The method of claim 1, wherein said compound is selected from the group of monoaminocyclohexanepentols (inosamines), diaminocyclohexanetetrols (inosadiamines), diaminocyclohexanetriols, stereoisomers thereof and enantiomers thereof, and pharmaceutically acceptable salts thereof.

18. The method of claim 17, wherein said compound is selected from the group of L-neo-inosamine, DL-epi-inosamine-2, streptamine and deoxystreptamine.

19. The method of claim 1, wherein said compound is a monomercapto-cyclohexanepentol or a stereoisomer or an enantiomer thereof

20. The method of claim 19, wherein said compound is L-1-deoxy-1-mercapto-8-O-methyl-chiro-inositol.

21. The method of claim 1, wherein said compound is scyllo-inositol.

22. The method of claim 1, wherein said compound is allo-inositol.

23. The method of claim 1, wherein said condition of the central or peripheral nervous system or systemic organ results in the deposition of proteins, protein fragments and peptides in beta-pleated sheats and/or fibrils and/or aggregates.

24. The method of claim 23, wherein said condition of the central or peripheral nervous system or systemic organ is selected from the group of:

Alzheimer'"'"'s disease, presenile and senile forms;

amyloid angiopathy;

mild cognitive impairment;

Alzheimer'"'"'s disease-related dementia;

tauopathy;

a-synucleinopathy;

Parkinson'"'"'s disease;

Amyotrophic Lateral Sclerosis;

motor neuron Disease;

Spastic paraplegia;

Huntington'"'"'s Disease, spinocerebellar ataxia, Freidrich'"'"'s Ataxia;

neurodegenerative diseases associated with intracellular and/or intraneuronal aggregates of proteins with polyglutamine, polyalanine or other repeats arising from pathological expansions of tri- or tetra-nucleotide elements within corresponding genes;

cerebrovascular diseases;

Down'"'"'s syndrome;

head trauma with post-traumatic accumulation of amyloid beta peptide;

Prion related disease;

Familial British Dementia;

Familial Danish Dementia;

Presenile Dementia with Spastic Ataxia;

Cerebral Amyloid Angiopathy, British Type;

Presenile Dementia With Spastic Ataxia Cerebral Amyloid Angiopathy, Danish Type;

Familial encephalopathy with neuroserpin inclusion bodies (FENIB);

Amyloid Polyneuropathy;

Inclusion Body myositis due to amyloid beta peptide;

Familial and Finnish Type Amyloidosis;

Systemic amyloidosis associated with multiple myeloma;

Familial Mediterranean Fever;

chronic infections and inflammations; and

Type II Diabetes Mellitus associate with islet amyloid polypeptide (IAPP).

25. The method of claim 24, wherein said condition of the central or peripheral nervous system or systemic organ is Alzheimer'"'"'s disease.

26. The method of claim 24, wherein said Alzheimer'"'"'s disease-related dementias is vascular or Alzheimer dementia.

27. The method of claim 24, wherein said tauopathy is selected from the group of argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with parkinsonism, Prion-related disease, Hallervorden-Spatz disease, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian Motor Neuron disease with neurofibrillary tangles, Pick'"'"'s disease, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, progressive supranuclear palsy, subacute sclerosing panencephalitis, and tangle only dementia.

28. The method of claim 24, wherein said ac-synucleinopathy is selected from the group of dementia with Lewy bodies, multiple system atrophy with glial cytoplasmic inclusions, Shy-Drager syndrome, striatonigral degeneration, olivopontocerebellar atrophy, neurodegeneration with brain iron accumulation type I, olfactory dysfunction, and amyotrophic lateral sclerosis.

29. The method of claim 24, wherein said condition of the central or peripheral nervous system or systemic organ is Parkinson'"'"'s disease.

30. The method of claim 29, wherein said Parkinson'"'"'s disease is familial.

31. The method of claim 29, wherein said Parkinson'"'"'s disease is non-familial

32. The method of claim 24, wherein said Motor Neuron Disease is associated with filaments and aggregates of neurofilament and/or superoxide dismutase proteins.

33. The method of claim 24, wherein said Spastic paraplegia is associated with defective function of chaperones and/or triple A proteins.

34. The method of claim 24, wherein said spinocerebellar ataxia is DRPLA or Machado-Joseph Disease.

35. The method of claim 24, wherein said Prion related disease is selected from the group of Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and variant Creutzfeldt-Jakob disease.

36. The method of claim 34, wherein said Amyloid Polyneuropathy is Senile amyloid polyneuropathy or Systemic Amyloidosis.

37. The method of claim 1, wherein said compound is administered at a dose of about 1 mg to about 1 g per kg of the weight of said subject.

38. The method of claim 37, wherein said compound is administered at a dose of about 1 mg to about 200 mg per kg of the weight of said subject.

39. The method of claim 37, wherein said compound is administered at a dose of about 10 mg to about 100 mg per kg of the weight of said subject.

40. The method of claim 37, wherein said compound is administered at a dose of about 30 mg to about 70 mg per kg of the weight of said subject.

69. The method of claim 24, wherein said condition of the central or peripheral nervous system or systemic organ is Parkinson'"'"'s disease.

70. The method of claim 69, wherein said Parkinson'"'"'s disease is familial.

71. The method of claim 69, wherein said Parkinson'"'"'s disease is non-familial

41. A method of preventing abnormal protein folding, abnormal protein aggregation, amyloid formation, deposition, accumulation, or persistence, or amyloid lipid interactions in a subject comprising administering to said subject a pharmaceutically effective amount of a compound having the following structure:

42. The method of claim 41, wherein said compound is said compound is a 1,2,3,4,5,6-cyclohexanehexol.

43. The method of claim 42, wherein said compounds is selected from the group of cis-, epi-, allo-, muco-, neo-, scyllo-, D-chiro- and L-chiro-inositols.

44. The method of claim 41, wherein said compound is a 1,2,3,4,5-cyclohexanepentol.

45. The method of claim 44, wherein said compound is a quercitol selected from the group of epi-, vibo-, scyllo-, allo-, talo-, gala-, cis-, muco-, neo-, proto-quercitols and enantiomers thereof.

46. The method of claim 41, wherein said compound is selected from the group of a cyclohexanetetrol, a cyclohexanetriol, stereoisomer of cyclohexanetetrol, stereoisimer of cyclohexanetriol, enantiomer of cyclohexanetetrol, and enantiomer of cyclohexanetriol.

47. The method of claim 41, wherein said compound is a pentahydroxycyclohexanone or a stereoisomer or an enantoimer thereof.

48. The method of claim 47, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

49. The method of claim 41, wherein said compound is a trihydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

50. The method of claim 49, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

51. The method of claim 41, wherein said compound is a pentahydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

52. The method of claim 51, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

53. The method of claim 41, wherein said compound is a trihydroxyxcyclohexanone or a stereoisomer or an enantiomer thereof.

54. The method of claim 53, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

55. The method of claim 41, wherein said compound is an 0-monomethyl-cyclohexanehexol or a stereoisomer or an enantiomer thereof.

56. The method of claim 55, wherein said compound is selected from the group of D-pinitol, L-quebrachitol and D-bomesitol.

57. The method of claim 41, wherein said compound is selected from the group of monoaminocyclohexanepentols (inosamines), diaminocyclohexanetetrols (inosadiamines), diaminocyclohexanetriols, tstereoisomers thereof and, enantiomers thereof, and pharmaceutically acceptable salts thereof.

58. The method of claim 57, wherein said compound is selected from the group of L-neo-inosamine, DL-epi-inosamine-2, streptamine and deoxystreptamine.

59. The method of claim 41, wherein said compound is a monomercapto-cyclohexanepentol or a stereoisomer or an enantiomer thereof

60. The method of claim 59, wherein said compound is 1L-1-deoxy-1-mercapto-8-O-methyl-chiro-inositol.

61. The method of claim 41, wherein said compound is scyllo-inositol.

62. The method of claim 41, wherein said compound is allo-inositol.

63. The method of claim 41, wherein said condition of the central or peripheral nervous system or systemic organ results in the deposition of proteins, protein fragments and peptides in beta-pleated sheats and/or fibrils and/or aggregates.

64. The method of claim 63, wherein said condition of the central or peripheral nervous system or systemic organ is selected from the group of:

Alzheimer'"'"'s disease, presenile and senile forms;

amyloid angiopathy;

mild cognitive impairment;

Alzheimer'"'"'s disease-related dementia;

tauopathy;

α

-synucleinopathy;

Parkinson'"'"'s disease;

Amyotrophic Lateral Sclerosis;

motor neuron Disease;

Spastic paraplagia;

Huntington'"'"'s Disease, spinocerebellar ataxia, Freidrich'"'"'s Ataxia;

neurodegenerative diseases associated with intracellular and/or intraneuronal aggregates of proteins with polyglutamine, polyalanine or other repeats arising from pathological expansions of tri- or tetra-nucleotide elements within corresponding genes;

cerebrovascular diseases;

Down'"'"'s syndrome;

head trauma with post-traumatic accumulation of amyloid beta peptide;

Prion related disease;

Familial British Dementia;

Familial Danish Dementia;

Presenile Dementia with Spastic Ataxia;

Cerebral Amyloid Angiopathy, British Type;

Presenile Dementia With Spastic Ataxia Cerebral Amyloid Angiopathy, Danish Type;

Familial encephalopathy with neuroserpin inclusion bodies (FENIB);

Amyloid Polyneuropathy;

Inclusion Body myositis due to amyloid beta peptide;

Familial and Finnish Type Amyloidosis;

Systemic amyloidosis associated with multiple myeloma;

Familial Mediterranean Fever;

chronic infections and inflammations; and

Type II Diabetes Mellitus associate with islet amyloid polypeptide (IAPP).

65. The method of claim 64, wherein said condition of the central or peripheral nervous system or systemic organ is Alzheimer'"'"'s disease.

66. The method of claim 64, wherein said Alzheimer'"'"'s disease-related dementias is vascular or Alzheimer dementia.

67. The method of claim 64, wherein said tauopathy is selected from the group of argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with parkinsonism, Prion-related disease, Hallervorden-Spatz disease, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian Motor Neuron disease with neurofibrillary tangles, Pick'"'"'s disease, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, progressive supranuclear palsy, subacute sclerosing panencephalitis, and tangle only dementia.

68. The method of claim 64, wherein said α

-synucleinopathy is selected from the group of dementia with Lewy bodies, multiple system atrophy with glial cytoplasmic inclusions, Shy-Drager syndrome, striatonigral degeneration, olivopontocerebellar atrophy, neurodegeneration with brain iron accumulation type I, olfactory dysfunction, and amyotrophic lateral sclerosis.

72. The method of claim 64, wherein said Motor Neuron Disease is associated with filaments and aggregates of neurofilament and/or superoxide dismutase proteins.

73. The method of claim 64, wherein said Spastic paraplagia is associated with defective function of chaperones and/or triple A proteins.

74. The method of claim 64, wherein said spinocerebellar ataxia is DRPLA or Machado-Joseph Disease.

75. The method of claim 64, wherein said Prion related disease is selected from the group of Creutzfeldt-Jakob disease, Gerstmann-Strä

ussler-Scheinker disease, and variant Creutzfeldt-Jakob disease.

76. The method of claim 64, wherein said Amyloid Polyneuropathy is Senile amyloid polyneuropathy or Systemic Amyloidosis.

77. The method of claim 41, wherein said compound is administered at a dose of about 1 mg to about 1 g per kg of the weight of said subject.

78. The method of claim 77, wherein said compound is administered at a dose of about 1 mg to about 200 mg per kg of the weight of said subject.

79. The method of claim 77, wherein said compound is administered at a dose of about 10 mg to about 100 mg per kg of the weight of said subject.

80. The method of claim 77, wherein said compound is administered at a dose of about 30 mg to about 70 mg per kg of the weight of said subject.

81. A method of causing the dissociation of abnormally aggregated proteins and/or dissolving or disrupting pre-formed or pre-deposited amyloid fibril or amyloid in a subject comprising administering to said subject a pharmaceutically effective amount of a compound having the following structure:

82. The method of claim 81, wherein said compound is said compound is a 1,2,3,4,5,6-cyclohexanehexol.

83. The method of claim 82, wherein said compounds is selected from the group of cis-, epi-, allo-, muco-, neo-, scyllo-, D-chiro- and L-chiro-inositols.

84. The method of claim 81, wherein said compound is a 1,2,3,4,5-cyclohexanepentol.

85. The method of claim 84, wherein said compound is a quercitol selected from the group of epi-, vibo-, scyllo-, allo-, talo-, gala-, cis-, muco-, neo-, proto-quercitols and enantiomers thereof.

86. The method of claim 81, wherein said compound is selected from the group of a cyclohexanetetrol, a cyclohexanetriol, stereoisomer of cyclohexanetetrol, stereoisimer of cyclohexanetriol, enantiomer of cyclohexanetetrol, and enantiomer of cyclohexanetriol.

87. The method of claim 81, wherein said compound is a pentahydroxycyclohexanone or a stereoisomer or an enantoimer thereof.

88. The method of claim 87, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-I and L-epi-inosose.

89. The method of claim 81, wherein said compound is a trihydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

90. The method of claim 89, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

91. The method of claim 81, wherein said compound is a pentahydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

92. The method of claim 91, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-I and L-epi-inosose.

93. The method of claim 81, wherein said compound is a trihydroxyxcyclohexanone or a stereoisomer or an enantiomer thereof.

94. The method of claim 93, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

95. The method of claim 81, wherein said compound is an O-monomethyl-cyclohexanehexol or a stereoisomer or an enantiomer thereof.

96. The method of claim 95, wherein said compound is selected from the group of D-pinitol, L-quebrachitol and D-bomesitol.

97. The method of claim 81, wherein said compound is selected from the group of monoaminocyclohexanepentols (inosamines), diaminocyclohexanetetrols (inosadiamines), diaminocyclohexanetriols, tstereoisomers thereof and, enantiomers thereof, and pharmaceutically acceptable salts thereof.

98. The method of claim 97, wherein said compound is selected from the group of L-neo-inosamine, DL-epi-inosamine-2, streptamine and deoxystreptamine.

99. The method of claim 81, wherein said compound is a monomercapto-cyclohexanepentol or a stereoisomer or an enantiomer thereof.

100. The method of claim 99, wherein said compound is 1L-1-deoxy-1-mercapto-8-O-methyl-chiro-inositol.

101. The method of claim 91, wherein said compound is scyllo-inositol.

102. The method of claim 81, wherein said compound is allo-inositol.

103. The method of claim 81, wherein said condition of the central or peripheral nervous system or systemic organ results in the deposition of proteins, protein fragments and peptides in beta-pleated sheats and/or fibrils and/or aggregates.

104. The method of claim 103, wherein said condition of the central or peripheral nervous system or systemic organ is selected from the group of:

Alzheimer'"'"'s (ii disease, presenile and senile forms;

amyloid angiopathy;

mild cognitive impairment;

Alzheimer'"'"'s disease-related dementia;

tauopathy;

α

-synucleinopathy;

Parkinson'"'"'s disease;

Amyotrophic Lateral Sclerosis;

motor neuron Disease;

Spastic paraplagia;

Huntington'"'"'s Disease, spinocerebellar ataxia, Freidrich'"'"'s Ataxia;

neurodegenerative diseases associated with intracellular and/or intraneuronal aggregates of proteins with polyglutamine, polyalanine or other repeats arising from pathological expansions of tri- or tetra-nucleotide elements within corresponding genes;

cerebrovascular diseases;

Down'"'"'s syndrome;

head trauma with post-traumatic accumulation of amyloid beta peptide;

Prion related disease;

Familial British Dementia;

Familial Danish Dementia;

Presenile Dementia with Spastic Ataxia;

Cerebral Amyloid Angiopathy, British Type;

Presenile Dementia With Spastic Ataxia Cerebral Amyloid Angiopathy, Danish Type;

Familial encephalopathy with neuroserpin inclusion bodies (FENIB);

Amyloid Polyneuropathy;

Inclusion Body myositis due to amyloid beta peptide;

Familial and Finnish Type Amyloidosis;

Systemic amyloidosis associated with multiple myeloma;

Familial Mediterranean Fever;

chronic infections and inflammations; and

Type II Diabetes Mellitus associate with islet amyloid polypeptide (IAPP).

105. The method of claim 104, wherein said condition of the central or peripheral nervous system or systemic organ is Alzheimer'"'"'s disease.

106. The method of claim 104, wherein said Alzheimer'"'"'s disease-related dementias is vascular or Alzheimer dementia.

107. The method of claim 104, wherein said tauopathy is selected from the group of argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with parkinsonism, Prion-related disease, Hallervorden-Spatz disease, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian Motor Neuron disease with neurofibrillary tangles, Pick'"'"'s disease, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, progressive supranuclear palsy, subacute sclerosing panencephalitis, and tangle only dementia.

108. The method of claim 104, wherein said ac-synucleinopathy is selected from the group of dementia with Lewy bodies, multiple system atrophy with glial cytoplasmic inclusions, Shy-Drager syndrome, striatonigral degeneration, olivopontocerebellar atrophy, neurodegeneration with brain iron accumulation type I, olfactory dysfunction, and amyotrophic lateral sclerosis.

109. The method of claim 84, wherein said condition of the central or peripheral nervous system or systemic organ is Parkinson'"'"'s disease.

110. The method of claim 109, wherein said Parkinson'"'"'s disease is familial.

111. The method of claim 109, wherein said Parkinson'"'"'s disease is non-familial

112. The method of claim 104, wherein said Motor Neuron Disease is associated with filaments and aggregates of neurofilament and/or superoxide dismutase proteins.

113. The method of claim 104, wherein said Spastic paraplagia is associated with defective function of chaperones and/or triple A proteins.

114. The method of claim 104, wherein said spinocerebellar ataxia is DRPLA or Machado-Joseph Disease.

115. The method of claim 104, wherein said Prion related disease is selected from the group of Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, 0 and variant Creutzfeldt-Jakob disease.

116. The method of claim 104, wherein said Amyloid Polyneuropathy is Senile amyloid polyneuropathy or Systemic Amyloidosis.

117. The method of claim 81, wherein said compound is administered at a dose of about 1 mg to about 1 g per kg of the weight of said subject.

118. The method of claim 117, wherein said compound is administered at a dose of about 1 mg to about 200 mg per kg of the weight of said subject.

119. The method of claim 117, wherein said compound is administered at a dose of about 10 mg to about 100 mg per kg of the weight of said subject.

120. The method of claim 117, wherein said compound is administered at a dose of about 30 mg to about 70 mg per kg of the weight of said subject.

121. A method of diagnosing the presence of abnormally folded or aggregated protein and/or amyloid fibril or amyloid in a subject comprising:

(a) administering to said subject a radioactive compound or compound tagged with a substance that emits a detectable signal in a quantity sufficient and under conditions to allow for the binding of said compound to the abnormally folded or aggregated protein and/or fibrils or amyloid, if present; and

(b) detecting the radioactivity or the signal from the compound bound to the abnormally folded or aggregated protein and/or fibrils or amyloid, thus diagnosing the presence of abnormally folded or aggregated protein and/or amyloid fibril or amyloid in said subject, wherein said compound has the following structure;

wherein each of R₁, R_1′

, R₂, R_2′

, R₃, R_3′

, R₄, R_4′

, R₅, R_5′

, R₆, and R_6′

is independently selected from the group of;

(a) hydrogen atom;

(b) NHR₇, wherein said R₇ is selected from the group of hydrogen;

C₂-C₁₀ acyl and C₁-C₁₀ alkyl;

(c) NR₈R₉, wherein said R₈ is C₂-C_{1 0} acyl or C₁-C₁₀ alkyl and said R₉ is C₂-C₁₀ acyl or C₁-C₁₀ alkyl;

(d) OR₁₀, wherein said R₁₀ is selected from the group of no group, hydrogen, C₂-C₁₀ acyl, C₁-C₁₀ alkyl and SO₃H;

(e) C₅-C₇ glycosyl;

(f) C₃-C₈ cycloalkyl optionally substituted with a substituent selected from the group of hydrogen, OH, NH₂, SH, OSO₃H and OPO₃H₂;

(g) SR₁₁, wherein R₁₁ is selected from the group of hydrogen, C₁-C₁₀ alkyl and O₃H;

(h) C₁-C₁₀ alkyl optionally substituted with a substituent selected from the group of hydrogen, OR₁₀, NHR₇, NR₈R₉ and SR₁₁; and

(i) C₃-C₈ cycloalkyl optionally substituted with a substituent selected from the group of hydrogen, OR₁₀, NHR₇, NR₈R₉ and SR₁₁,

providing that the compound is not myo-inositol.

122. The method of claim 121, wherein said compound is said compound is a 1,2,3,4,5,6-cyclohexanehexol.

123. The method of claim 122, wherein said compounds is selected from the group of cis-, epi-, allo-, muco-, neo-, scyllo-, D-chiro- and L-chiro-inositols.

124. The method of claim 121, wherein said compound is a 1,2,3,4,5-cyclohexanepentol.

125. The method of claim 124, wherein said compound is quercitol selected from the group of epi-, vibo-, scyllo-, allo-, talo-, gala-, cis-, muco-, neo-, proto-quercitols and enantiomers thereof.

126. The method of claim 121, wherein said compound is selected from the group of a cyclohexanetetrol, a cyclohexanetriol, stereoisomer of cyclohexanetetrol, stereoisimer of cyclohexanetriol, enantiomer of cyclohexanetetrol, and enantiomer of cyclohexanetriol.

127. The method of claim 121, wherein said compound is a pentahydroxycyclohexanone or a stereoisomer or an enantoimer thereof.

128. The method of claim 127, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

129. The method of claim 121, wherein said compound is a trihydroxyxcyclohexanone, or a stereoisomer or an enantiomer thereof.

130. The method of claim 129, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

131. The method of claim 121, wherein said compound is a pentahydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

132. The method of claim 131, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-1 and L-epi-inosose.

133. The method of claim 121, wherein said compound is a trihydroxyxcyclohexanone or a stereoisomer or an enantiomer thereof.

134. The method of claim 133, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

135. The method of claim 121, wherein said compound is an O-monomethyl-cyclohexanehexol or a stereoisomer or an enantiomer thereof.

136. The method of claim 135, wherein said compound is selected from the 0 group of D-pinitol, L-quebrachitol and D-bomesitol.

137. The method of claim 121, wherein said compound is selected from the group of monoaminocyclohexanepentols (inosamines), diaminocyclohexanetetrols (inosadiamines), diaminocyclohexanetriols, tstereoisomers thereof and, enantiomers thereof, and pharmaceutically acceptable salts thereof.

138. The method of claim 137, wherein said compound is selected from the group of L-neo-inosamine, DL-epi-inosamine-2, streptamine and deoxystreptamine.

139. The method of claim 121, wherein said compound is a monomercapto-cyclohexanepentol or a stereoisomer or an enantiomer thereof

140. The method of claim 139, wherein said compound is 1L-1-deoxy-1-mercapto-8-O-methyl-chiro-inositol.

141. The method of claim 121, wherein said compound is scyllo-inositol.

142. The method of claim 121, wherein said compound is allo-inositol.

143. The method of claim 121, wherein said condition of the central or peripheral nervous system or systemic organ results in the deposition of proteins, protein fragments and peptides in beta-pleated sheats and/or fibrils and/or aggregates.

144. The method of claim 143, wherein said condition of the central or peripheral nervous system or systemic organ is selected from the group of:

Alzheimer'"'"'s disease, presenile and senile forms;

amyloid angiopathy;

mild cognitive impairment;

Alzheimer'"'"'s disease-related dementia;

tauopathy;

α

-synucleinopathy;

Parkinson'"'"'s disease;

Amyotrophic Lateral Sclerosis;

motor neuron Disease;

Spastic paraplagia;

Huntington'"'"'s Disease, spinocerebellar ataxia, Freidrich'"'"'s Ataxia;

neurodegenerative diseases associated with intracellular and/or intraneuronal aggregates of proteins with polyglutamine, polyalanine or other repeats arising from pathological expansions of tri- or tetra-nucleotide elements within corresponding genes;

cerebrovascular diseases;

Down'"'"'s syndrome;

head trauma with post-traumatic accumulation of amyloid beta peptide;

Prion related disease;

Familial British Dementia;

Familial Danish Dementia;

Presenile Dementia with Spastic Ataxia;

Cerebral Amyloid Angiopathy, British Type;

Presenile Dementia With Spastic Ataxia Cerebral Amyloid Angiopathy, Danish Type;

Familial encephalopathy with neuroserpin inclusion bodies (FENIB);

Amyloid Polyneuropathy;

Inclusion Body myositis due to amyloid beta peptide;

Familial and Finnish Type Amyloidosis;

Systemic amyloidosis associated with multiple myeloma;

Familial Mediterranean Fever;

chronic infections and inflammations; and

Type II Diabetes Mellitus associate with islet amyloid polypeptide (IAPP).

145. The method of claim 144, wherein said condition of the central or peripheral nervous system or systemic organ is Alzheimer'"'"'s disease.

146. The method of claim 144, wherein said Alzheimer'"'"'s disease-related dementias is vascular or Alzheimer dementia.

147. The method of claim 144, wherein said tauopathy is selected from the group of argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with parkinsonism, Prion-related disease, Hallervorden-Spatz disease, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian Motor Neuron disease with neurofibrillary tangles, Pick'"'"'s disease, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, progressive supranuclear palsy, subacute sclerosing panencephalitis, and tangle only dementia.

148. The method of claim 144, wherein said α

-synucleinopathy is selected from the group of dementia with Lewy bodies, multiple system atrophy with glial cytoplasmic inclusions, Shy-Drager syndrome, striatonigral degeneration, olivopontocerebellar atrophy, neurodegeneration with brain iron accumulation type I , olfactory dysfunction, and amyotrophic lateral sclerosis.

149. The method of claim 144, wherein said condition of the central or peripheral nervous system or systemic organ is Parkinson'"'"'s disease.

150. The method of claim 149, wherein said Parkinson'"'"'s disease is familial.

151. The method of claim 149, wherein said Parkinson'"'"'s disease is non-familial

152. The method of claim 144, wherein said Motor Neuron Disease is associated with filaments and aggregates of neurofilament and/or superoxide dismutase proteins.

153. The method of claim 144, wherein said Spastic paraplagia is associated with defective function of chaperones and/or triple A proteins.

154. The method of claim 144, wherein said spinocerebellar ataxia is DRPLA or Machado-Joseph Disease.

155. The method of claim 144, wherein said Prion related disease is selected from the group of Creutzfeldt-Jakob disease, Gerstmann-Strä

ussler-Scheinker disease, and variant Creutzfeldt-Jakob disease.

156. The method of claim 144, wherein said Amyloid Polyneuropathy is Senile amyloid polyneuropathy or Systemic Amyloidosis.

157. The method of claim 121, wherein said compound is administered at a dose of about 1 mg to about 1 g per kg of the weight of said subject.

158. The method of claim 157, wherein said compound is administered at a dose of about 1 mg to about 200 mg per kg of the weight of said subject.

159. The method of claim 121, wherein said detectable signal is a fluorescent signal.

160. The method of claim 121, wherein said detectable signal is a radioactive signal.

161. A method of diagnosing the presence of abnormally folded or aggregated protein and/or amyloid fibril or amyloid in a subject comprising:

(a) collecting a sample from said subject;

(b) contacting said sample with a radioactive compound or compound tagged with a substance that emits a detectable signal under conditions to allow the binding of said compound to the abnormally folded or aggregated protein and/or amyloid fibril or amyloid if present; and

(c) detecting the radioactivity or the signal from the compound bound to the abnormally folded or aggregated protein and/or fibrils or amyloid, thus diagnosing the presence of abnormally folded or aggregated protein and/or amyloid fibril or amyloid in said subject, wherein said compound has the following structure;

wherein each of R₁, R_1′

, R₂, R_2′

, R₃, R_3′

, R₄, R_4′

, R₅, R_5′

, R₆, and R_6′

is independently selected from the group of;

(a) hydrogen atom;

(b) NHR₇, wherein said R₇ is selected from the group of hydrogen;

C₂-C₁₀ acyl and C₁-C₁₀ alkyl;

(c) NR₈R₉, wherein said R₈ is C₂-C₁₀ acyl or C₁-C₁₀ alkyl and said R₉ is C₂-C₁₀ acyl or C₁-C₁₀ alkyl;

(d) OR₁₀, wherein said R₁₀ is selected from the group of no group, hydrogen, C₂-C₁₀ acyl, C₁-C₁₀ alkyl and SO₃H;

(e) C₅-C₇ glycosyl;

(f) C₃-C₈ cycloalkyl optionally substituted with a substituent selected from the group of hydrogen, OH, NH₂, SH, OSO₃H and OPO₃H₂;

(g) SR₁₁, wherein R₁₁ is selected from the group of hydrogen, C₁-C₁₀ alkyl and O₃H;

(h) C₁-C₁₀ alkyl optionally substituted with a substituent selected from the group of hydrogen, OR₁₀, NHR₇, NR₈R₉ and SR₁₁; and

(i) C₃-C₈ cycloalkyl optionally substituted with a substituent selected from the group of hydrogen, OR₁₀, NHR₇, NR₈R₉ and SR₁₁,

providing that the compound is not myo-inositol.

162. The method of claim 161, wherein said compound is said compound is a 1,2,3,4,5,6-cyclohexanehexol.

163. The method of claim 162, wherein said compounds is selected from the group of cis-, epi-, allo-, muco-, neo-, scyllo-, D-chiro- and L-chiro-inositols.

164. The method of claim 161, wherein said compound is a 1,2,3,4,5-cyclohexanepentol.

165. The method of claim 164, wherein said compound is a quercitol selected from the group of epi-, vibo-, scyllo-, allo-, talo-, gala-, cis-, muco-, neo-, proto-quercitols and enantiomers thereof.

166. The method of claim 161, wherein said compound is selected from the group of a cyclohexanetetrol, a cyclohexanetriol, stereoisomer of cyclohexanetetrol, stereoisimer of cyclohexanetriol, enantiomer of cyclohexanetetrol, and enantiomer of cyclohexanetriol.

167. The method of claim 161, wherein said compound is a pentahydxycyclohexanone, a stereoisomer or an enantoimer thereof.

168. The method of claim 167, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-I and L-epi-inosose.

169. The method of claim 161, wherein said compound is a trihydroxyxcyclohexanone, or a stereoisomer or an enantiomer thereof.

170. The method of claim 169, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

171. The method of claim 161, wherein said compound is a pentahydroxycyclohexanone, or a stereoisomer or an enantiomer thereof.

172. The method of claim 171, wherein said compound is an inosose selected from the group of scyllo-inosose, L-chiro-inosose-I and L-epi-inosose.

173. The method of claim 161, wherein said compound is a trihydroxyxcyclohexanone or a stereoisomer or an enantiomer thereof.

174. The method of claim 163, wherein said compound is (−

)-1-deoxy-scyllo-inosose.

175. The method of claim 161, wherein said compound is an O-monomethyl-cyclohexanehexol or a stereoisomer or an enantiomer thereof.

176. The method of claim 175, wherein said compound is selected from the group of D-pinitol, L-quebrachitol and D-bomesitol.

177. The method of claim 161, wherein said compound is selected from the group of monoaminocyclohexanepentols (inosamines), diaminocyclohexanetetrols (inosadiamines), diaminocyclohexanetriols, tstereoisomers thereof and, enantiomers thereof, and pharmaceutically acceptable salts thereof.

178. The method of claim 177, wherein said compound is selected from the group of L-neo-inosamine, DL-epi-inosamine-2, streptamine and deoxystreptamine.

179. The method of claim 161, wherein said compound is a monomercapto-cyclohexanepentol or a stereoisomer or an enantiomer thereof

180. The method of claim 179, wherein said compound is 1L-1-deoxy-1-mercapto-8-O-methyl-chiro-inositol.

181. The method of claim 161, wherein said compound is scyllo-inositol.

182. The method of claim 161, wherein said compound is allo-inositol.

183. The method of claim 161, wherein said condition of the central or peripheral nervous system or systemic organ results in the deposition of proteins, protein fragments and peptides in beta-pleated sheats and/or fibrils and/or aggregates.

184. The method of claim 183, wherein said condition of the central or peripheral nervous system or systemic organ is selected from the group of:

Alzheimer'"'"'s disease, presenile and senile forms;

amyloid angiopathy;

mild cognitive impairment;

Alzheimer'"'"'s disease-related dementia;

tauopathy;

α

-synucleinopathy;

Parkinson'"'"'s disease;

Amyotrophic Lateral Sclerosis;

motor neuron Disease;

Spastic paraplagia;

Huntington'"'"'s Disease, spinocerebellar ataxia, Freidrich'"'"'s Ataxia;

neurodegenerative diseases associated with intracellular and/or intraneuronal aggregates of proteins with polyglutamine, polyalanine or other repeats arising from pathological expansions of tri- or tetra-nucleotide elements within corresponding genes;

cerebrovascular diseases;

Down'"'"'s syndrome;

head trauma with post-traumatic accumulation of amyloid beta peptide;

Prion related disease;

Familial British Dementia;

Familial Danish Dementia;

Presenile Dementia with Spastic Ataxia;

Cerebral Amyloid Angiopathy, British Type;

Presenile Dementia With Spastic Ataxia Cerebral Amyloid Angiopathy, Danish Type;

Familial encephalopathy with neuroserpin inclusion bodies (FENIB);

Amyloid Polyneuropathy;

Inclusion Body myositis due to amyloid beta peptide;

Familial and Finnish Type Amyloidosis;

Systemic amyloidosis associated with multiple myeloma;

Familial Mediterranean Fever;

chronic infections and inflammations; and

Type II Diabetes Mellitus associate with islet amyloid polypeptide (IAPP).

185. The method of claim 184, wherein said condition of the central or peripheral nervous system or systemic organ is Alzheimer'"'"'s disease.

186. The method of claim 184, wherein said Alzheimer'"'"'s disease-related dementias is vascular or Alzheimer dementia.

187. The method of claim 184, wherein said tauopathy is selected from the group of argyrophilic grain dementia, corticobasal degeneration, dementia pugilistica, diffuse neurofibrillary tangles with calcification, frontotemporal dementia with parkinsonism, Prion-related disease, Hallervorden-Spatz disease, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian Motor Neuron disease with neurofibrillary tangles, Pick'"'"'s disease, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, progressive supranuclear palsy, subacute sclerosing panencephalitis, and tangle only dementia.

188. The method of claim 184, wherein said a-synucleinopathy is selected from the group of dementia with Lewy bodies, multiple system atrophy with glial cytoplasmic inclusions, Shy-Drager syndrome, striatonigral degeneration, olivopontocerebellar atrophy, neurodegeneration with brain iron accumulation type I, olfactory dysfunction, and amyotrophic lateral sclerosis.

189. The method of claim 184, wherein said condition of the central or peripheral nervous system or systemic organ is Parkinson'"'"'s disease.

190. The method of claim 189, wherein said Parkinson'"'"'s disease is familial.

191. The method of claim 189, wherein said Parkinson'"'"'s disease is non-familial

192. The method of claim 184, wherein said Motor Neuron Disease is associated with filaments and aggregates of neurofilament and/or superoxide dismutase proteins.

193. The method of claim 184, wherein said Spastic paraplagia is associated with defective function of chaperones and/or triple A proteins.

194. The method of claim 184, wherein said spinocerebellar ataxia is DRPLA or Machado-Joseph Disease.

195. The method of claim 184, wherein said Prion related disease is selected from the group of Creutzfeldt-Jakob disease, Gerstmann-Strä

ussler-Scheinker disease, and variant Creutzfeldt-Jakob disease.

196. The method of claim 184, wherein said Amyloid Polyneuropathy is Senile amyloid polyneuropathy or Systemic Amyloidosis.

197. The method of claim 161, wherein said detectable signal is a fluorescent signal.

198. The method of claim 161, wherein said detectable signal is a radioactive signal.

199. The method of claim 161, wherein said detectable signal is an enzyme-linked immunosorbent assay signal

200. The method of claim 161, wherein said sample is whole blood.

201. The method of claim 161, wherein said sample is plasma.