TauRx Therapeutics

Last updated
TauRx Therapeutics
IndustryPharmaceuticals, Life Sciences
Founded Singapore (2002)
FounderClaude Wischik
K. M. Seng
Headquarters
Singapore   OOjs UI icon edit-ltr-progressive.svg
,
Singapore   OOjs UI icon edit-ltr-progressive.svg
Number of locations
Singapore and Aberdeen, Scotland
Key people
Claude Wischik, Executive Chairman
Shay Way Seng, Managing Director
Website TauRx Therapeutics

TauRx Therapeutics Ltd is a life sciences/pharmaceutical company incorporated in Singapore with primary research facilities and operations in Aberdeen, Scotland. [1] [2]

Contents

The company was co-founded in 2002 by the late gynecologist, surgeon and venture capitalist K. M. Seng and Claude Wischik, Professor of Old Age Psychiatry at the University of Aberdeen, Scotland, who is currently the company's Executive Chairman.

The company's protein aggregation inhibitors target the underlying pathology of dementia, with the aim of modifying or halting disease progression. Their lead compound, LMTX, targets aggregation of tau and is believed to act on synuclein, TDP-43 and huntingtin protein. Its primary development in Alzheimer's disease is focused in its activity as a Tau aggregation inhibitor (TAI). [3] [4] [5] [6]

History

In 1988, while at Cambridge University, Wischik and coworkers discovered that abnormal fibres of tau protein form inside nerve cells in patients with Alzheimer's disease, and that their aggregation into tau tangles correlates to the development of dementia. In 1997, Wischik and his team moved to the University of Aberdeen, where they continued their research into tau pathology and protein aggregation inhibition. In 2002, the company was formed as a spin-out of the University of Aberdeen.

Methylthioninium chloride – a first generation tau aggregation inhibitor (TAI) was used in Phase 2 clinical trials in Alzheimer's. [7] [8] The Phase 2 compared 3 dosages of methylthioninium chloride). [9]

In 2012, Phase 3 clinical trials were starting with leucomethylthioninium salts (LMTX) for mild and moderate Alzheimer's disease and behavioral variant FTD (bvFTD).

LMTX

LMTX is a stable anhydrous reduced form of methylthioninium chloride. [10] : fig 1A  (Chloride is replaced by bromide or methanesulfonate.) One of these is undergoing a phase 3 clinical trial for safety and efficacy in mild Alzheimer's disease as "TRx0237". [11] The results of the trial were released in July 2016. As a whole, patients who participated in the trial did not show significant benefits from receiving the LMTX.

TauRx has presented a post-hoc subgroup analysis suggesting that a small group of patients in the trial, who were taking only LMTX without any other Alzheimer's medication, did show significant improvement. [11] [12] However, this characterization of the secondary analysis results has been challenged on statistical grounds, and based on the fact that an inappropriate placebo group was used in the comparison. [13]

Related Research Articles

<span class="mw-page-title-main">Frontotemporal dementia</span> Types of dementia involving the frontal or temporal lobes

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as behavioral or language disorders with gradual onsets. Common signs and symptoms include significant changes in social and personal behavior, apathy, blunting of emotions, and deficits in both expressive and receptive language. Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms.

<span class="mw-page-title-main">Donepezil</span> Medication used for dementia

Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth or via a transdermal patch.

<span class="mw-page-title-main">Galantamine</span> Neurological medication

Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.

A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis by improving blood lipid levels. At least three medications within this class have failed to demonstrate a beneficial effect.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.

Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of daily living. MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimer's disease. It includes both memory and non-memory impairments. The cause of the disorder remains unclear, as well as both its prevention and treatment, with some 50 percent of people diagnosed with it going on to develop Alzheimer's disease within five years. The diagnosis can also serve as an early indicator for other types of dementia, although MCI may remain stable or even remit.

<span class="mw-page-title-main">Latrepirdine</span> Antihistamine drug

Latrepirdine is an antihistamine drug which has been used clinically in Russia since 1983.

<i>scyllo</i>-Inositol Chemical compound

scyllo-Inositol is one of the stereoisomers of inositol. It is also known as scyllitol, cocositol, quercinitol, and 1,3,5/2,4,6-hexahydroxycyclohexane. scyllo-Inositol is a naturally occurring plant sugar alcohol found most abundantly in the coconut palm.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Solanezumab is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector for patients with Alzheimer's disease. The drug originally attracted extensive media coverage proclaiming it a breakthrough, but it has failed to show promise in Phase III trials.

<span class="mw-page-title-main">Acetylcholinesterase inhibitor</span> Drugs that inhibit acetylcholinesterase

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

<span class="mw-page-title-main">Losmapimod</span> Chemical compound

Losmapimod (GW856553X) is an investigational drug being developed by Fulcrum Therapeutics for the treatment of facioscapulohumeral muscular dystrophy (FSHD); a phase III clinical trial is pending approval. Losmapimod selectively inhibits enzymes p38α/β mitogen-activated protein kinases (MAPKs), which are modulators of DUX4 expression and mediators of inflammation.

<span class="mw-page-title-main">Rivastigmine</span> Chemical compound

Rivastigmine is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.

Crenezumab is a fully humanized monoclonal antibody against human 1-40 and 1-42 beta amyloid, which is being investigated as a treatment of Alzheimer's disease. Crenezumab is highly homologous to solanezumab, another monoclonal antibody targeting amyloid-β peptides. In June 2022, the US National Institutes of Health announced that the drug failed as a medication for early-onset Alzheimer's disease following the results of a decade-long clinical trial.

Methanesulfonyl fluoride (MSF) has long been known to be a potent inhibitor of acetylcholinesterase (AChE), the enzyme that regulates acetylcholine, an important neurotransmitter in both the central and peripheral nervous systems.

<span class="mw-page-title-main">Tideglusib</span> Chemical compound

Tideglusib is a potent and irreversible small molecule glycogen synthase kinase 3 (GSK-3) inhibitor.

<span class="mw-page-title-main">Verubecestat</span> Chemical compound

Verubecestat (MK-8931) was an experimental drug for the treatment of Alzheimer's disease. It is an inhibitor of beta-secretase 1 (BACE1), which, after initial promise proved disappointing.

Lecanemab, sold under the brand name Leqembi, is a monoclonal antibody medication used for the treatment of Alzheimer's disease. Lecanemab is an amyloid beta-directed antibody. It is given via intravenous infusion. The most common side effects of lecanemab include headache, infusion-related reactions and amyloid-related imaging abnormalities, a side effect known to occur with the class of antibodies targeting amyloid.

<span class="mw-page-title-main">Phenserine</span> Chemical compound

Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.

<span class="mw-page-title-main">Buntanetap</span> Chemical compound

Buntanetap is an orally-administered small molecule inhibitor of several neurotoxic proteins that is under investigation in the treatment of Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy and Parkinson's disease. It is the (+) enantiomer of phenserine, as the (-) enantiomer also has unwanted anticholinergic effects. It is currently in phase III trials for the treatment of Parkinson's.

References

  1. ↑ Whalen, Jeanne (2012-11-09). "An outcast among peers gains traction on Alzheimer's cure". Wall Street Journal . Retrieved 2013-03-27.
  2. ↑ Marchione, Marilynn (2008-07-30). "Experimental Alzheimer's drug shows early promise". Associated Press . Retrieved 2008-07-31.[ permanent dead link ]
  3. ↑ Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR (October 1996). "Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines". Proceedings of the National Academy of Sciences of the United States of America. 93 (20): 11213–8. Bibcode:1996PNAS...9311213W. doi: 10.1073/pnas.93.20.11213 . PMC   38310 . PMID   8855335.
  4. ↑ Wischik CM, Lai RY, Harrington CR (1997). "Modelling prion-like processing of tau protein in Alzheimer's disease for pharmaceutical development". In Brandt R, Avila J, Kosik KS (eds.). Brain Microtubule Associated Proteins: Modifications in Disease. Amsterdam: Harwood Acad. Publ. pp. 185–241. ISBN   978-90-5702-173-2.
  5. ↑ Wischik CM, Wischik DJ, Storey JM, Harrington CR (2010). "Beta-Amyloid, Tau Protein and Glucose Metabolism". In Martinez A (ed.). Emerging Drugs and Targets for Alzheimer's Disease. Vol. 1. Cambridge: Royal Society of Chemistry. pp. 210–232. ISBN   978-1-84973-064-8.
  6. ↑ Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, Hasegawa M (March 2005). "Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins". The Journal of Biological Chemistry. 280 (9): 7614–23. doi: 10.1074/jbc.M408714200 . PMID   15611092.
  7. ↑ Wischik CM, Bentham P, Wischik DJ, Seng KM (2008). "Tau aggregation inhibitor (TAI) therapy slows disease progression in mild and moderate Alzheimer's disease over 50 weeks". Alzheimer's & Dementia . 4: T167. doi:10.1016/j.jalz.2008.05.438. S2CID   54291555 . Retrieved 2012-10-01.
  8. ↑ Wilkinson, Emma (2006-07-29). "Alzheimer's drug 'halts' decline". BBC . Retrieved 2008-07-29.
  9. ↑ Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, Storey JM, Kook KA, Harrington CR (2015). "Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease". Journal of Alzheimer's Disease. 44 (2): 705–20. doi: 10.3233/JAD-142874 . hdl: 2164/4205 . PMID   25550228.
  10. ↑ Complex Disposition of Methylthioninium Redox Forms Determines Efficacy in Tau Aggregation Inhibitor Therapy for Alzheimer’s Disease
  11. 1 2 "Safety and efficacy study evaluating TRx0237 in subjects with mild Alzheimer's disease". ClinicalTrials.gov. 2 November 2015. Retrieved 2 November 2015.
  12. ↑ Coghlan, Andy (28 July 2016). "Alzheimer's drug that failed trial may still slow disease". New Scientist . Retrieved 29 July 2016.
  13. ↑ Fagan, Tom (29 July 2016). "In First Phase 3 Trial, the Tau Drug LMTM Did Not Work. Period". Alzforum . Retrieved 31 July 2016.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.