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New light on bipolar treatment drugs

21 April 2009

STRICT EMBARGO UNTIL TUESDAY, APRIL 21 2009, 00.15 HRS EASTERN DAYLIGHT TIME (05:15 HRS BRITISH SUMMER TIME)

Lithium has been established for more than 50 years as one of the most effective treatments for bipolar mood disorder.

However, scientists have never been entirely sure exactly how it operates in the human brain.

Now, new research from Cardiff University scientists suggests a mechanism for how Lithium works, opening the door for potentially more effective treatments.

Laboratory tests on cells have shown that Lithium affects a molecule called PIP3 that is important in controlling brain cell signalling. Lithium suppresses the production of inositol, a simple sugar from which PIP3 is made.

Lithium inhibits inositol monophosphatase (IMPase) an enzyme required for making inositol. Importantly, this research shows that increasing the amount of IMPase causes higher levels of PIP3. This can then be reduced by lithium treatment.

High levels of IMPA2, a gene for a variant of IMPase, has previously been linked to bipolar mood disorder. This new result suggests that Lithium could counteract the changes in IMPA2.

Professor Adrian Harwood of Cardiff School of Biosciences, who led the research, said: "We still cannot say definitively how Lithium can help stabilise bipolar disorder. However, our research does suggest a possible pathway for its operation. By better understanding Lithium, we can learn about the genetics of bipolar disorder and develop more potent and selective drugs.

"Further, altered PIP3 signalling is linked to other disorders, including epilepsy and autism, so this well established drug could be used to treat other conditions. Research into Lithium could become very important over the next few years."

Lithium is currently under clinical trial for the treatment of neurogenerative disorder amyotrophic lateral sclerosis (ALS)

The research, funded by the Wellcome Trust, is published in the journal Disease Models and Mechanisms.

ENDS

Notes to Editors:

The paper, The mood stabiliser lithium suppresses PIP3 signalling in

Dictyostelium and human cells, is published online today by The Journal of Disease Models and Mechanisms. The authors are Dr Jason S. King, Dr Regina Teo, Dr Jonathan Ryves, Dr Jonathan V. Reddy, Mr Owen Peters, Mr Ben Orabi, Dr Oliver Hoeller, Dr Robin S. B. Williams and Professor Adrian J. Harwood

For news media only: IF REPORTING ON THIS STORY, PLEASE MENTION THE JOURNAL OF DISEASE MODELS & MECHANISMS AS THE SOURCE AND, IF REPORTING ONLINE, PLEASE CARRY A LINK TO: http://dmm.biologists.org

Full text of the article is available ON REQUEST. To obtain a copy contact Donna Perry, Disease Models & Mechanisms,

Cambridge, UK. Tel: +44 (0)1223 433319 or email donna@biologists.com

Secondary contact: Tel (615) 364-6152 or email n.garbarini@biologists.com

Cardiff University

Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research intensive universities. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans.

Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise in research and research-led teaching encompasses: the humanities; the natural, physical, health, life and social sciences; engineering and technology; preparation for a wide range of professions; and a longstanding commitment to lifelong learning.

Visit the University website at: www.cardiff.ac.uk

The Wellcome Trust

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk

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17.4.09

BIOSI2Lithium

Further Information:

For further information, please contact

Professor Adrian Harwood,

School of Biosciences,

Cardiff University,

02920 879358

email: harwoodaj@cardiff.ac.uk

Stephen Rouse,

Public Relations Office,

Cardiff University.

029 2087 5596

e-mail: RouseS@cardiff.ac.uk