TauRx Therapeutics Ltd.

Singapore, Singapore

TauRx Therapeutics Ltd.

Singapore, Singapore
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Reilly T.J.,Biomedical Imaging Center | Staff R.T.,Royal Infirmary | Ahearn T.S.,Biomedical Imaging Center | Bentham P.,University of Birmingham | And 2 more authors.
Behavioural Brain Research | Year: 2011

Aberrant motor behaviour (AMB) in Alzheimer's disease shares behavioural correlates with obsessive compulsive disorder (OCD). We investigated whether AMB was also comparable in terms of metabolic activity in the orbitofrontal cortex (OFC), an area shown to be hyperactive in OCD. In this study 135 patients meeting research criteria for Alzheimer's disease were identified from a database of patients recruited as part of a phase II drug trial. These patients were assessed using the Neuropsychiatric Inventory, the Alzheimer's disease assessment scale, cognitive subscale and perfusion SPECT performed with 99Tcm hexamethylpropyleneamine oxime. Regions of interest were created for orbitofrontal cortices and basal ganglia. In 35 patients with AMB, adjusted tracer uptake was greater in the OFC. This reached statistical significance in right superior, left superior, right medial and left medial orbital gyri (p<0.05). The association between AMB and hyperactivity in the OFC remained significant after adjusting for the presence of anxiety. These results parallel the OFC hypermetabolism consistently seen in OCD. One model of OCD, proposes that dysfunctional interactions between frontal regions, including the OFC, produce the characteristic symptoms of OCD. The behaviour is though to be brought about by a perceived incompleteness of performing a task and is caused by an error in normal reward signals initiated upon task completion. These finding indicate that AMB in Alzheimer's disease are brought about by the same mechanistic failure. © 2011 Elsevier B.V.


Wischik C.M.,TauRx Therapeutics Ltd. | Wischik C.M.,University of Aberdeen | Harrington C.R.,TauRx Therapeutics Ltd. | Harrington C.R.,University of Aberdeen | And 2 more authors.
Biochemical Pharmacology | Year: 2014

Many trials of drugs aimed at preventing or clearing β-amyloid pathology have failed to demonstrate efficacy in recent years and further trials continue with drugs aimed at the same targets and mechanisms. The Alzheimer neurofibrillary tangle is composed of tau and the core of its constituent filaments are made of a truncated fragment from the repeat domain of tau. This truncated tau can catalyse the conversion of normal soluble tau into aggregated oligomeric and fibrillar tau which, in turn, can spread to neighbouring neurons. Tau aggregation is not a late-life process and onset of Braak stage 1 peaks in people in their late 40s or early 50s. Tau aggregation pathology at Braak stage 1 or beyond affects 50% of the population over the age of 45. The initiation of tau aggregation requires its binding to a non-specific substrate to expose a high affinity tau-tau binding domain and it is self-propagating thereafter. The initiating substrate complex is most likely formed as a consequence of a progressive loss of endosomal-lysosomal processing of neuronal proteins, particularly of membrane proteins from mitochondria. Mutations in the APP/presenilin membrane complex may simply add to the age-related endosomal-lysosomal processing failure, bringing forward, but not directly causing, the tau aggregation cascade in carriers. Methylthioninium chloride (MTC), the first identified tau aggregation inhibitor (TAI), offers an alternative to the amyloid approach. Phase 3 trials are underway with a novel stabilized reduced form of methylthioninium (LMTX) that has improved tolerability and absorption. © 2014 The Authors.


Baddeley T.C.,University of Aberdeen | McCaffrey J.,Salamandra LLC | Storey J.M.D.,University of Aberdeen | Cheung J.K.S.,University of Aberdeen | And 5 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2015

Methylthioninium (MT) is a tau aggregation inhibitor with therapeutic potential in Alzheimer's disease (AD). MT exists in equilibrium between reduced [leucomethylthioninium (LMT)] and oxidized (MT+) forms; as a chloride salt [methylthioniniumchloride (MTC), "methylene blue"], it is stabilized in its MT+ form. Although the results of a phase 2 study of MTC in 321 mild/moderate AD subjects identified a 138-mg MT/day dose as the minimum effective dose on cognitive and imaging end points, further clinical development of MT was delayed pending resolution of the unexpected lack of efficacy of the 228-mg MT/day dose. We hypothesized that the failure of dose response may depend on differences known at the time in dissolution in simulated gastric and intestinal fluids of the 100-mg MTC capsules used to deliver the 228-mg dose and reflect previously unsuspected differences in redox processing of MT at different levels in the gut. The synthesis of a novel chemical entity, LMTX (providing LMT in a stable anhydrous crystalline form), has enabled a systematic comparison of the pharmacokinetic properties of MTC and LMTX in preclinical and clinical studies. The quantity of MT released in water or gastric fluid within 60 minutes proved in retrospect to be an important determinant of clinical efficacy. A further factor was a dose-dependent limitation in the ability to absorb MT in the presence of food when delivered in the MT+ form as MTC. A model is presented to account for the complexity of MT absorption, which may have relevance for other similar redox molecules. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics


Harrington C.R.,University of Aberdeen | Harrington C.R.,TauRx Therapeutics Ltd. | Storey J.M.D.,TauRx Therapeutics Ltd. | Storey J.M.D.,University of Aberdeen | And 14 more authors.
Journal of Biological Chemistry | Year: 2015

Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated fromAD brain tissues at 0.16 μM. The Ki value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 μM. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 μM) that is required to arrest progression ofADon clinical and imaging end points and the minimum brain concentration (0.13 μM) required to reverse behavioral deficits and pathology in Tau transgenic mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.


Trademark
TauRx Therapeutics Ltd. | Date: 2015-12-22

Pharmaceutical and medical preparations for use in relation to neurological diseases and disorders, neurodegenerative diseases and disorders, blood disorders, infectious diseases and malaria; chemical preparations for medical and pharmaceutical purposes for use in relation to neurological diseases and disorders, neurodegenerative diseases and disorders, blood disorders, infectious diseases and malaria; none of the aforesaid being pharmaceutical preparations and substances intended for the prevention and treatment of bone/skeletal diseases. Surgical and medical apparatus and instruments for use in general surgery; medical apparatus and instruments for facilitating the analysis of biological and chemical matter in the field of genetic testing, namely, blood, brain, urine, cerebrospinal fluid analysis and testing apparatus; medical testing apparatus for the analysis of biological and chemical matter, namely, apparatus for blood, brain, urine and cerebrospinal fluid analysis and tests; surgical and medical apparatus and instruments for facilitating the analysis of biological and chemical matter, namely, apparatus for blood, brain, urine and cerebrospinal fluid analysis and tests. Retail store services and online retail store services in connection with the sale of pharmaceutical and medical preparations, chemical preparations for medical and pharmaceutical purposes, surgical and medical apparatus and instruments, apparatus for carrying out tests for medical purposes, scientific and medical apparatus for use in tests; consulting services in the field of medical practice management for others in the fields of neurodegenerative and neurological diseases and disorders, malaria and infectious diseases. Medical, biological, biotechnological, genetic, and pharmaceutical research, design and development services and laboratory research services in the fields of drugs, pharmaceuticals and medicines; research, development and design of drugs and medicine; drug discovery services; laboratory and medical laboratory research and development services relating to drugs, pharmaceuticals and medicines; exploitation of scientific research and technology, namely, providing advice and information relating to scientific and technological research, researching and developing new products in the fields of drugs, pharmaceuticals and medicines, and scientific research and development services in the fields of drug development, clinical trial design, patient recruitment, drug testing, clinical data management, data analysis, statistical analysis, patient selection, clinical diagnosis and diagnostic testing; preparation of reports of scientific and medical research concerning drugs, pharmaceuticals, medicines, genetics, biology and biotechnology; development and design of medical or scientific prognostic and diagnostic apparatus and instruments; consultancy and information services relating to all of the aforesaid. Medical clinic services; health resort services in the nature of medical clinics; services for the provision of medical facilities; medical services; medical advisory services; medical diagnostic testing, monitoring and reporting services; providing medical information, consultancy and advisory services; medical screening information services featuring reminder alerts regarding medical examinations that individuals should undergo for preventative care purposes; medical screening services in the fields of neurodegenerative and neurological diseases and disorders, malaria and infectious diseases; medical services featuring health assessment surveys; consultancy and information services relating to all the aforesaid.


Trademark
TauRx Therapeutics Ltd. | Date: 2013-03-13

pharmaceutical and medical preparations for use in relation to neurological diseases and disorders, neurodegenerative diseases and disorders, infectious diseases and malaria; chemical preparations for medical and pharmaceutical purposes for prevention, diagnosis, and treatment of neurological diseases and disorders, neurodegenerative diseases and disorders, infectious diseases and malaria.


Trademark
TauRx Therapeutics Ltd | Date: 2011-11-01

Computer software for use in analysis and diagnosis of medical conditions for facilitating research in the fields of science, medicines, drugs, pharmaceuticals, biology, biotechnology, bioinformatics, clinical development and statistics, apart from cost optimization of prescription drug plans, prescription drug alternatives, or drug utilization; computer software for use in laboratory and diagnostic instruments, namely, computer software for use in the analysis and diagnosis of medical conditions; scientific and teaching apparatus and instruments in the nature of prerecorded CD ROMs and computer disks containing electronic publications concerning pharmaceutical drug development, namely, test reports, magazines, and manuals in the fields of pre-clinical, clinical, and pharmaceutical research and drug discovery and drug research; computer servers. Blood testing apparatus; medical diagnostic instruments for the analysis of bodily fluids; medical apparatus and instruments for use in surgery; medical apparatus for introducing pharmaceutical preparations into the body; medical diagnostic apparatus for detecting neurodegenerative disease. Printed matter, namely, booklets, hand books, journals, manuals, magazines, periodicals, and pamphlets, all in the field of neurodegenerative diseases and methods of treating and developing treatments for the same. Retail store services featuring pharmaceutical and medical preparations, chemical preparations for medical and pharmaceutical purposes, scientific, measuring and teaching apparatus and instruments, computer software, surgical and medical apparatus and instruments, apparatus for carrying out tests for medical purposes, scientific and medical apparatus for use in tests, and printed matter, books, journals, magazines, leaflets, publications, printed tests, written reports in the field of medical and pharmaceutical research, apart from cost optimization of prescription drug plans, prescription drug alternatives, or drug utilization. Pharmaceutical drug development services; scientific research and consultation in the field of clinical trials; consulting services in the fields of biotechnology, pharmaceutical research and development, laboratory testing, diagnostics, and pharmacogenetics; biological research. Medical services featuring health assessment surveys; providing information and consultancy relating to the aforesaid medical services.


Trademark
TauRx Therapeutics Ltd | Date: 2011-11-01

Pharmaceutical preparations for the treatment of diseases, illnesses and ailments in humans and animals, namely, infectious and parasitic diseases, neoplasms, blood disorders, mental disorders, disorders of the nervous system and sensory organs, musculoskeletal system disorders, genitourinary system disorders, communicable diseases, neurological diseases, and psychological conditions; chemical preparations for medical and pharmaceutical purposes for the treatment of diseases, illnesses and ailments in humans and animals, namely, infectious and parasitic diseases, neoplasms, blood disorders, mental disorders, disorders of the nervous system and sensory organs, musculoskeletal system disorders, genitourinary system disorders, communicable diseases, neurological diseases, and psychological conditions; chemical preparations for medical and pharmaceutical purposes, namely, diagnostic preparations for use in diagnosing diseases, illnesses, and ailments in humans and animals, namely, infectious and parasitic diseases, neoplasms, blood disorders, mental disorders, disorders of the nervous system and sensory organs, musculoskeletal system disorders, genitourinary system disorders, communicable diseases, neurological diseases, and psychological conditions.

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