Materials and methods relating to protein aggregation in neurodegenerative disease

1. A method for the treatment of Alzheimer's Disease, which method comprises administering to a subject in need thereof a medicament composition comprising a diaminophenothiazine, wherein the diaminophenothiazine has been pre-reduced such that it is present in at least 80, 90, 95 or 99% reduced (leuco-) form,

wherein the diaminophenothiazine is pre-reduced by addition of an exogenous reducing agent,

and wherein the reduced form is lyophilised,

wherein the pre-reduced diaminophenothiazine has the formula:

wherein R 1 , R 3 , R 4 , R 6 , R 7 and R 9 are independently selected from hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted alkyl, haloalkyl or alkoxy;

R 5 is hydrogen; and

each R 10 and R 11 is independently selected from hydrogen, hydroxy, carboxy, substituted or unsubstituted alkyl, haloalkyl or alkoxy;

or is a pharmaceutically acceptable salt thereof.

2. A method as claimed in claim 1 wherein the reduced form is stabilized in the reduced state by addition of a stabilizing agent.

3. A method as claimed in claim 2 wherein the reduced form is lyophilized with the stabilizing agent.

4. A method as claimed in claim 1 wherein the medicament composition further comprises one or more additives selected from the group consisting of pharmaceutically-acceptable excipients, carriers and buffers.

5. A method as claimed in claim 4 wherein the medicament composition is a slow release formulation.

6. A method as claimed in claim 1 wherein R 1 , R 3 , R 4 , R 6 , R 7 and R 9 are independently selected from -hydrogen, —CH 3 , —C 2 H 5 or —C 3 H 7 ; each R 10 and R 11 are independently selected from hydrogen, —CH 3 , —C 2 H 5 or —C 3 H 7 ; and R 5 is hydrogen, —CH 3 , —C 2 H 5 or —C 3 H 7 .

7. A method as claimed in claim 1 wherein the diaminophenothiazine has 0, 2, 3 or 4 methyl groups around the diaminophenothiazine nucleus.

8. A method as claimed in claim 1 wherein the diaminophenothiazine is asymmetrically methylated.

9. A method as claimed in claim 8 wherein the diaminophenothiazine is selected from the group consisting of tolonium chloride, Azure A, Azure B and thionine.

10. A method as claimed in claim 8 wherein the diaminophenothiazine is selected from the group consisting of Methylene Blue, Toluidine Blue O and 1,9-Dimethylmethylene Blue.

11. A method as claimed in claim 3 wherein the stabilizing agent is ascorbic acid.

12. A method as claimed in claim 1 wherein the treatment comprises administering a therapeutically effective amount of the medicament composition to a patient in need thereof.

13. A method as claimed in claim 12 wherein the treatment comprises administering the medicament composition to a patient in need thereof three times a day, and wherein the medicament composition comprises 20 mg, 50 mg or 100 mg diaminophenothiazine combined with 2× mg ratio of ascorbic acid such that more than 90% diaminophenothiazine is reduced prior to ingestion.

14. A method as claimed in claim 12 wherein the treatment comprises administering to a patient in need thereof a diaminophenothiazine which is thionine in a daily dosage of between 1 and 1000 mg optionally divided into 1 to 8 unit doses.

15. A method as claimed in claim 12 wherein the treatment comprises administering to a patient in need thereof a diaminophenothiazine which is methylene blue in a daily dosage of from about 3.2 to about 3.5 mg/kg body weight.