Administration and dosage of diaminophenothiazines

1. A method of therapeutic treatment of a neurodegenerative disorder of protein aggregation in a subject,

which method comprises orally administering once per day to said subject a methylthioninium (MT)-containing compound,

wherein said administration provides a total daily dose of between 0.5 and 20 mg of MT to the subject per day,

wherein the MT compound is a compound of the following formula (“LMTX”):

wherein each of H n A and H n B (where present) are protic acids which may be the same or different,

and wherein p=1 or 2; q=0 or 1; n=1 or 2; (p+q)×n=2,

and wherein said neurodegenerative disorder is selected from the list consisting of:

Alzheimer's disease;

Pick's disease, progressive supranuclear palsy, frontotemporal dementia, FTD with parkinsonism linked to chromosome 17, frontotemporal lobar degeneration syndromes;

disinhibition-dementia-parkinsonism-amyotrophy complex, pallido-ponto-nigral degeneration, Guam-ALS syndrome, pallido nigro luysian degeneration, cortico-basal degeneration, dementia with argyrophilic grains, dementia pugilistica or chronic traumatic encephalopathy, Down's syndrome, subacute sclerosing panencephalitis, Niemann-Pick disease, type C, Sanfilippo syndrome type B, or a myotonic dystrophy DM1 or DM2;

Huntington's disease, spinal bulbar muscular atrophy, dentatorubropallidoluysian atrophy or spinocerebellar ataxias;

A TDP-43 proteinopathy which is FTLD-TDP;

Parkinson's disease, dementia with Lewy bodies and multiple system atrophy;

Hereditary cerebral angiopathy;

Amyotrophic lateral sclerosis; and

familial encephalopathy with neuronal inclusion bodies.

2. The method as claimed in claim 1 wherein the total daily dosage is 2 to 15 mg; or 3 to 10 mg.

3. The method as claimed in claim 1 wherein;

(a) the compound has the following formula, where HA and HB are different mono-protic acids:

or

(b) compound has the following formula:

wherein each of H n X is a protic acid; or

(c) the compound has the following formula and H 2 A is a di-protic acid:

4. The method as claimed in claim 1 wherein the compound has the following formula and is a bis-monoprotic acid:

5. The method as claimed in claim 1 wherein the or each protic acid is an inorganic acid.

6. The method as claimed in claim 1 wherein the or each protic acid is an organic acid.

7. The method as claimed in claim 6 wherein the or each protic acid is selected from H 2 CO 3 , CH 3 COOH, methanesulfonic acid, 1,2-ethanedisulfonic acid, ethansulfonic acid, naphthalenedisulfonic acid, and p-toluenesulfonic acid.

8. The method as claimed in claim 7 wherein the compound is LMTM:

9. The method as claimed in claim 8 wherein the total daily dose of LMTM is around 0.8 to 33 mg/day, more preferably 6 to 12 mg/day of LMTM total.

10. The method as claimed in claim 9 wherein the dose of LMTM is around 9 mg/once per day.

11. The method as claimed in claim 1 wherein the compound is selected from the list consisting of:

12. A method of prophylactic treatment of a neurodegenerative disorder of protein aggregation in a subject,

which method comprises orally administering once per day to said patient a methylthioninium (MT) containing compound,

wherein said administration provides a total daily dose of between 0.5 and 20 mg of MT to the subject per day,

wherein the MT compound is a compound of the following formula (“LMTX”):

wherein each of H n A and H n B (where present) are protic acids which may be the same or different,

and wherein p=1 or 2; q=0 or 1; n=1 or 2; (p+q)×n=2,

and wherein said neurodegenerative disorder is selected from the list consisting of:

Alzheimer's disease;

Pick's disease, progressive supranuclear palsy, frontotemporal dementia, FTD with parkinsonism linked to chromosome 17, frontotemporal lobar degeneration syndromes; disinhibition-dementia-parkinsonism-amyotrophy complex, pallido-ponto-nigral degeneration, Guam-ALS syndrome, pallido nigro luysian degeneration, cortico-basal degeneration, dementia with argyrophilic grains, dementia pugilistica or chronic traumatic encephalopathy, Down's syndrome, subacute sclerosing panencephalitis, Niemann-Pick disease, type C, Sanfilippo syndrome type B, or a myotonic dystrophy DM1 or DM2;

Huntington's disease, spinal bulbar muscular atrophy, dentatorubropallidoluysian atrophy or spinocerebellar ataxias;

A TDP-43 proteinopathy which is FTLD-TDP;

Parkinson's disease, dementia with Lewy bodies and multiple system atrophy;

Hereditary cerebral angiopathy;

Amyotrophic lateral sclerosis; and

familial encephalopathy with neuronal inclusion bodies.

13. The method as claimed in claim 1 wherein the subject has not historically received treatment with an acetylcholinesterase inhibitor or an N-methyl-D-aspartate receptor antagonist.

14. The method as claimed in claim 1 wherein the subject has historically received treatment with an acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist, but ceased that medication at least 1, 2, 3, 4, 5, 6, 7, or 8 weeks prior to treatment with the MT containing compound.

15. The method as claimed in claim 1 wherein the subject is selected as one who is receiving treatment with an acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist,

wherein said treatment with the acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist is discontinued prior to treatment with the MT containing compound.

16. A pharmaceutical composition comprising an MT compound of the following formula (“LMTX”):

wherein each of H n A and H n B (where present) are protic acids which may be the same or different,

and wherein p=1 or 2; q=0 or 1; n=1 or 2; (p+q)×n=2, and a pharmaceutically acceptable carrier or diluent, in the form of a dosage unit,

wherein the amount of MT in the composition or unit is 2 to 9 mg.

17. The composition as claimed in claim 16 which is a tablet or a capsule.

18. The composition as claimed in claim 17 which comprises about any of: 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, or 15 mg of LMTM: