Abstract: Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: R1 and R9 are independently selected from: —H; C1-4alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4 alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4 alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

Abstract: The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of a acetylcholinesterase levels.

Abstract: The invention provides novel dosing regimens for Leuco-Methylthioninium (LMT) compounds which maximise the proportion of subjects in which the MT concentration will exceed concentrations in which therapeutic efficacy in relation to treatment of neurodegenerative disorders such as Alzheimer's disease and rontotemporal dementias can be achieved, while maintaining a desirable clinical profile. Also provided are LMT-containing dosage units and other compositions.

Abstract: The invention provides novel dosing regimens for Leuco-Methylthioninium (LMT) compounds which maximise the proportion of subjects in which the MT concentration will exceed concentrations in which therapeutic efficacy in relation to treatment of neurodegenerative disorders such as Alzheimer's disease and rontotemporal dementias can be achieved, while maintaining a desirable clinical profile. Also provided are LMT-containing dosage units and other compositions.

Abstract: A method for predicting a patient or patient cohort's cognition score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). The method comprises obtaining data relating to a plurality of patients or patient cohorts, the data including information relating to the longitudinal trajectories of the plurality of patients', or patient cohorts', ADAS-Cog score over time, each patient or patient cohort having undergone a treatment plan selected from a plurality of treatment plans; encoding the data into a tensor across patients or patient cohorts, time and treatment plan; generating a synthetic model of a target patient or target patient cohort using a machine learning process and the tensor; and predicting an ADAS-Cog score of the target patient or target patient cohort under a target treatment plan selected from the plurality of treatment plans, using the synthetic model.

Abstract: Disclosed are compounds of general formula (I): and pharmaceutically acceptable salts thereof, formulations, methods and uses in, for example, the treatment of disease.

Abstract: The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of acetylcholinesterase levels.

Abstract: Disclosed are compounds of general formula (I): and pharmaceutically acceptable salts thereof, formulations, methods and uses in, for example, the treatment of disease.

Abstract: Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: R1 and R9 are independently selected from: —H; C1-4alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4 alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4 alkyl; C2-4 alkenyl; and halogenated C1-4 alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

Abstract: Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

Abstract: Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: R1 and R9 are independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

Abstract: Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

Abstract: The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of a acetylcholinesterase levels.

Abstract: The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of acetylcholinesterase levels.

Abstract: T he present invention provides methods of treating COV-ID-19 in a subject using methylthioninium compounds.

Abstract: The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of acetylcholinesterase levels.

Abstract: The present invention provides methods of treating COVID-19 in a subject using methylthioninium compounds.

Abstract: The present invention provides methods of alleviating hypoxemia in a subject through oral administration of a methylthioninium compound.

Abstract: The invention provides novel dosing regimens for Leuco-Methylthioninium (LMT) compounds which maximise the proportion of subjects in which the MT concentration will exceed concentrations in which therapeutic efficacy in relation to treatment of neurodegenerative disorders such as Alzheimer's disease and rontotemporal dementias can be achieved, while maintaining a desirable clinical profile. Also provided are LMT-containing dosage units and other compositions.

Abstract: The present invention relates generally to methods of treatment of Alzheimer's Disease or Mild Cognitive Impairment which are adapted to avoid negative interactions between combinations of therapeutics. In particular there are disclosed such methods of treatment in which the order of therapeutics is actively controlled to mitigate homeostatic downregulation prior to administration of active, for example disease modifying, therapeutic agents. In certain embodiments therapy with symptomatic treatments (such as modifiers of the activity of acetylcholine or glutamate neurotransmitters) may subsequently be combined with the disease modifying or other active treatment. The invention also applies the findings in relation to homeostatic downregulation to novel methods of clinical trial design.