The biopharmaceutical company Noscira* is conducting a clinical trial of a new drug, tideglusib**, as a potential treatment for Progressive Supranuclear Palsy. Tideglusib is also being tested in trials for Alzheimer's disease.
Previously, tideglusib was tested on 160 healthy people, both young and old, in Phase I studies, and was found to be well tolerated. In addition, a study with 30 Alzheimer's Disease patients dosed for 20 weeks has provided safety and tolerability data in patients.
In animal studies (using transgenic mice) tideglusib has been found to improve cognitive performance and to reduce amyloid deposits, tau hyperphosphorylation, neuroinflammation, and neuronal loss - all of which are factors associated with Alzheimer's disease.
Tideglusib is the only compound reported to date that is capable of acting on all of the histopathological lesions associated with Alzheimer's disease. That tideglusib has been shown to affect tau phosphorylation, a feature of PSP as well as Alzheimer's disease, is the reason for thinking it may also have potential in the treatment of PSP.
Tideglusib obtained official designation as an orphan medicinal product for the treatment of Progressive Supranuclear Palsy in October 2009 in Europe and in the United States. In addition, fast track designation was obtained from the FDA in September 2010. These designations facilitate the interaction with regulatory authorities to optimise development plans for the granting of a marketing authorisation.
In addition, if significant benefits of the product are observed, these designations facilitate access to special procedures to accelerate the availability of the product in the market.
The tideglusib PSP Study, TAUROS study
Official title: A double-blind, placebo-controlled, randomized, parallel-group study evaluating the safety, tolerability and efficacy of two different oral doses of NP031112, a GSK-3 inhibitor, versus placebo in the treatment of patients with mild to moderate Progressive Supranuclear Palsy.
Purpose: To determine if tideglusib is safe and effective in the treatment of mild to moderate PSP.
The study: Participants in the study were randomized to receive 600mg tideglusib, 800mg tideglusib, or a placebo for 52 weeks. Recruitment has been completed.
Study completion date: End of 2011.
Participating centres: In the USA, Germany, Spain and UK. In the UK, three Centres, based in Liverpool, Newcastle and London are participating. As of October 2010 fourteen patients have been recruited in three UK Centres.
How is tideglusib expected to work?
PSP is thought to be caused by a brain protein called tau sticking together and forming neurofibrillary tangles. These tangles build up in brain cells, damaging different areas of the brain.
Tideglusib is expected to work in PSP and Alzheimer's disease by blocking an enzyme called glycogen synthase kinase-3β (GSK-3). GSK-3 is one of the main factors that make the tau protein become ‘sticky', forming the neurofibrillary tangles. By blocking GSK-3, tideglusib is expected to reduce the amount of tau protein sticking together, thereby reducing the damage to brain cells.
Both lithium and tideglusib act on the enzyme GSK-3, but it is hoped that tideglusib will not have the problematic toxicity of lithium. The recent safety and toxicity trial with lithium as a potential treatment for PSP was terminated because of lithium's adverse effects on patients.
Tideglusib is the only GSK-3 inhibitor under clinical development.
Dr Angela Wilson, The PSP Association's Director of Medical Awareness and Research, said:
The Noscira tideglusib trial is a really exciting step forward in our quest to find a much needed effective treatment for PSP. Tideglusib is a new drug and on the basis of the work undertaken so far looks promising. The drug must be safe to give to patients and that is one of the aspects that the current trial involving more than 100 PSP patients at centres across the United States and Europe is setting out to establish. The trial is also designed to evaluate efficacy of the compound. This aspect of the work will take around a year. We are still some way from having an effective treatment for PSP but Noscira's investment in PSP research is a much welcomed development and will help move us closer to our goal."
*Noscira, a subsidiary of the Zeltia Group (Spain's leading biotechnology and chemical company) is a biopharmaceutical company devoted to the research and development of innovative drugs for the treatment and prevention of diseases of the nervous system. Since its formation in 2000, Noscira has focused its activity on Alzheimer's disease and has two clinical compounds (tideglusib and NP-61) in the pipeline for treating Alzheimer's disease. For more information, visit www.noscira.com
**The international non-proprietary name of the active ingredient is "tideglusib". The company code is NP031112 and NP-12 was the commonly used name. The drug is also known as Nypta® and Zentylor TM.
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