17 Jun 2008 12:03
17th June 2008 Immediate Release
ReGen Therapeutics Plc
Zolpidem shown to improve cognitive and motor function in stroke subject by reducing pathological slow-wave brain activity.
ReGen Therapeutics Plc ('ReGen' or the 'Company') announces that collaborators at Aston University, Birmingham UK have significantly clarified the basis of zolpidem's beneficial effects in brain injured subjects using pharmaco-magnetoencephalography (MEG) brain imaging. Zolpidem but not placebo or other sedative drugs, reduced slow-wave brain activity, an effect which coincided with marked improvements in cognitive and motor function. The details of this study have been reported online in Nature Precedings *. ReGen has filed a new patent application around this important discovery.
Brain imaging studies (single photon emission computed tomography - SPECT scanning) and several hundred clinical case studies have previously shown that zolpidem can improve cognitive and motor function in brain damaged individuals. This led to the hypothesis that zolpidem 'reawakens' functionally dormant brain regions. However, before this investigation by Aston University a neuronal mechanism by which these benefits are achieved had not been demonstrated.
Aston University's research was carried out on a subject who had suffered a stroke several years previously. The subject presented with fluent conversational speech but had difficulties comprehending certain words, reduced sensory perception and abnormal gait.
When given a non-sedative dose of zolpidem, the subject showed marked improvements in cognition (including IQ and motor function) to such an extent that a single daily dose provided symptomatic relief lasting for up to eight hours. These cognitive and motor improvements were observed approximately 40 minutes after zolpidem administration. The increased functionality was coincident with the reduction of pathological theta (4-10Hz) and beta (15-30Hz) frequency brain waves in and around areas of brain lesion.
Commenting on the results of this study Dr. Stephen Hall - lead investigator, Aston University said
"For a number of years it has been known that various neurological conditions including Parkinson's disease, Alzheimer's and brain trauma have been associated with exaggerated slow-wave activity. These findings suggest that zolpidem is unique in its ability to reduce this pathological oscillatory activity. As such it seems reasonable to suggest that zolpidem could have significant therapeutic potential in conditions where these abnormal brainwaves are a feature."
Percy Lomax, ReGen Chairman and CEO added
"It has long been our view that there was something unique about zolpidem that meant the benefits we have seen in treating brain trauma cases could not be achieved by other common sedative drugs. There is still a lot more work to do but this study goes a considerable way to validating that belief and bolstering our patent position in these large areas of unmet medical need."
*http://precedings.nature.com/documents/1966/version/1
For further information:
Percy Lomax
ReGen Therapeutics Plc
Tel No 020 7153 4920
Roland Cornish/Felicity Geidt
Beaumont Cornish
Tel No 020 7628 3396
David Scott/Nick Bealer
Alexander David
Tel No 020 7448 9800
Adrian Duffield/Jon Davies
College Hill Associates
Tel No 020 7457 2020
Notes to Editors:
ReGen and the Zolpidem Project
The sedative zolpidem (marketed by Sanofi-Aventis under the trade names Stilnox™ and Ambien™) has been used for the last twenty years as a hypnotic/sedative by millions of people.
Several years ago Dr Wally Nel, a General Practitioner in South Africa, discovered that zolpidem promoted remarkable recoveries in some patients who were treated with it for insomnia, following traumatic brain injury and stroke. In a case report published in a South African medical journal in 2000, Dr Nel and his co-worker Dr Ralf Clauss described how approximately fifteen minutes after an oral dose of zolpidem was administered to a patient who had suffered a road traffic accident three years previously, he awoke from his semi-comatose condition and remained awake for the next 3-4 hours and when drug action subsided he returned to his previous state. That same patient is now awake for up to 10 hours a day after eight years of daily treatment with zolpidem. Further studies in Dr Nel's clinic have now shown that many subjects with brain-injury caused in various ways and with various degrees of severity have consistent and reproducible improvement in their clinical features when given zolpidem.
While Dr Nel continued his work in South Africa, Dr Clauss moved to the UK, where he teamed up with Dr Andrew Sutton (medical consultant to ReGen). Together with Dr Nel, they formed Sciencom Ltd and filed an international patent application covering this new use for zolpidem. This patent has since been approved in South Africa and is still pending in other countries.
In February 2006, ReGen Therapeutics Plc acquired the entire share capital of Sciencom and with it the rights to the company's patent application and the rights to continue to develop its zolpidem project.
ReGen believes that both a clear "therapeutic need" and a significant commercial opportunity exist for new, low-dose, non-sedating formulations of zolpidem, to enable this important clinical benefit to be optimally delivered to a diverse range of patients.
In August 2007, ReGen reported on a Clinical Study, which confirmed that a 2.5mg novel formulation of zolpidem is non-sedating when used on conscious, fully perceptive, ambulant patients having various debilities as a consequence of brain damage. It was performed in collaboration with the Company's subsidiary, Guildford Clinical Pharmacology Unit Limited and investigators at the Walko Medical Centre in Springs, South Africa where the 'antidormancy' effect of zolpidem was first discovered.
The study compared various single doses of a novel sublingual spray formulation (placebo, 2.5mg, 5mg, 10mg) with an existing tablet formulation (placebo, 10mg) in terms of the onset and degree of sedation. It also looked for preliminary signs of efficacy. The results showed that a 2.5mg spray was no more sedating than a placebo. The 10mg and 5mg sprays induced sedation in a dose responsive manner and the spray showed faster onset of action (sedative effect) than the tablet. The 5mg spray induced the same peak level of sedation as the 10mg tablet - 15 minutes compared with 90 minutes respectively. ReGen is planning a further 'proof of concept' study in stroke patients to show that an effective and non-sedating multiple dose regimen is practical. Should this trial be successful ReGen will look for a licensing partner. The Company estimates the current market for the use of zolpidem in 'the rehabilitation from brain trauma' to be worth US$4.3 billion.
Note 2:
The 'Waking Pill' clip is on the BBC website:
http://news.bbc.co.uk/player/nol/newsid_7070000/newsid_7071400/7071449.stm?bw=bb&mp=wm&news=1&nol_storyid=7071449&bbcws=1